Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

BACKGROUND: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF. METHODS: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488). FINDINGS: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48). INTERPRETATION: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. FUNDING: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

Fluid Intake in Critically Ill Patients: The "Save Useless Fluids For Intensive Resuscitation" Multicenter Prospective Cohort Study.

OBJECTIVES: Patients at risk of adverse effects related to positive fluid balance could benefit from fluid intake optimization. Less attention is paid to nonresuscitation fluids. We aim to evaluate the heterogeneity of fluid intake at the initial phase of resuscitation. DESIGN: Prospective multicenter cohort study. SETTING: Thirty ICUs across France and one in Spain. PATIENTS: Patients requiring vasopressors and/or invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All fluids administered by vascular or enteral lines were recorded over 24 hours following admission and were classified in four main groups according to their predefined indication: fluids having a well-documented homeostasis goal (resuscitation fluids, rehydration, blood products, and nutrition), drug carriers, maintenance fluids, and fluids for technical needs. Models of regression were constructed to determine fluid intake predicted by patient characteristics. Centers were classified according to tertiles of fluid intake. The cohort included 296 patients. The median total volume of fluids was 3546 mL (interquartile range, 2441-4955 mL), with fluids indisputably required for body fluid homeostasis representing 36% of this total. Saline, glucose-containing high chloride crystalloids, and balanced crystalloids represented 43%, 27%, and 16% of total volume, respectively. Whatever the class of fluids, center of inclusion was the strongest factor associated with volumes. Compared with the first tertile, the difference between the volume predicted by patient characteristics and the volume given was +1.2 ± 2.0 L in tertile 2 and +3.0 ± 2.8 L in tertile 3. CONCLUSIONS: Fluids indisputably required for body fluid homeostasis represent the minority of fluid intake during the 24 hours after ICU admission. Center effect is the strongest factor associated with the volume of fluids. Heterogeneity in practices suggests that optimal strategies for volume and goals of common fluids administration need to be developed.

Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion.

OBJECTIVE: Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. METHODS: This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. RESULTS: Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage. CONCLUSIONS: Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Delphi Process for Validation of Fluid Treatment Algorithm for Critically Ill Pediatric Trauma Patients.

INTRODUCTION: While intravenous fluid therapy is essential to re-establishing volume status in children who have experienced trauma, aggressive resuscitation can lead to various complications. There remains a lack of consensus on whether pediatric trauma patients will benefit from a liberal or restrictive crystalloid resuscitation approach and how to optimally identify and transition between fluid phases. METHODS: A panel was comprised of physicians with expertise in pediatric trauma, critical care, and emergency medicine. A three-round Delphi process was conducted via an online survey, with each round being followed by a live video conference. Experts agreed or disagreed with each aspect of the proposed fluid management algorithm on a five-level Likert scale. The group opinion level defined an algorithm parameter's acceptance or rejection with greater than 75% agreement resulting in acceptance and greater than 50% disagreement resulting in rejection. The remaining were discussed and re-presented in the next round. RESULTS: Fourteen experts from five Level 1 pediatric trauma centers representing three subspecialties were included. Responses were received from 13/14 participants (93%). In round 1, 64% of the parameters were accepted, while the remaining 36% were discussed and re-presented. In round 2, 90% of the parameters were accepted. Following round 3, there was 100% acceptance by all the experts on the revised and final version of the algorithm. CONCLUSIONS: We present a validated algorithm for intavenous fluid management in pediatric trauma patients that focuses on the de-escalation of fluids. Focusing on this time point of fluid therapy will help minimize iatrogenic complications of crystalloid fluids within this patient population.

Physical and Chemical Compatibility of Medications Commonly Used in Critically Ill Patients With Balanced Crystalloids: A Systematic Review.

OBJECTIVE: Evaluate available evidence of physical and/or chemical compatibility of commonly used medications in critically ill patients with balanced crystalloids. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were queried from inception to September 2022. STUDY SELECTION AND DATA EXTRACTION: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies reporting physical and/or chemical compatibility data between 50 selected medications and balanced crystalloids were included. A previously designed tool to assess risk of bias was adapted for use. DATA SYNTHESIS: Twenty-nine studies encompassing 39 (78%) medications and 188 unique combinations with balanced crystalloids were included. Combinations included 35 (70%) medications with lactated Ringer's, 26 (52%) medications with Plasma-Lyte, 10 (20%) medications with Normosol, and one (2%) medication with Isolyte. Studies commonly evaluated physical and chemical compatibility (55.2%). More medications were evaluated via Y-site than admixture. Incompatibilities were identified in 18% of combinations comprising 13 individual drugs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This systematic review evaluates the compatibility of select critical care medications with balanced crystalloid solutions. Results may be used as a tool to guide clinicians on balanced crystalloid compatibility, potentially increasing ubiquitous use and reducing patient exposure to normal saline. CONCLUSION AND RELEVANCE: Data are limited regarding chemical/physical compatibility of commonly used medications in critically ill patients with balanced crystalloids. Additional compatibility studies are warranted, particularly methodologically rigorous studies assessing Plasma-Lyte, Normosol, and Isolyte. Of the evaluated medications, there was a low frequency of incompatibilities with balanced crystalloids.

Trends in pre-hospital volume resuscitation of blunt trauma patients: a 15-year analysis of the British (TARN) and German (TraumaRegister DGU®) National Registries.

INTRODUCTION: Fluid resuscitation has long been a cornerstone of pre-hospital trauma care, yet its optimal approach remains undetermined. Although a liberal approach to fluid resuscitation has been linked with increased complications, the potential survival benefits of a restrictive approach in blunt trauma patients have not been definitively established. Consequently, equipoise persists regarding the optimal fluid resuscitation strategy in this population. METHODS: We analysed data from the two largest European trauma registries, the UK Trauma Audit and Research Network (TARN) and the German TraumaRegister DGU® (TR-DGU), between 2004 and 2018. All adult blunt trauma patients with an Injury Severity Score > 15 were included. We examined annual trends in pre-hospital fluid resuscitation, admission coagulation function, and mortality rates. RESULTS: Over the 15-year study period, data from 68,510 patients in the TARN cohort and 82,551 patients in the TR-DGU cohort were analysed. In the TARN cohort, 3.4% patients received pre-hospital crystalloid fluids, with a median volume of 25 ml (20-36 ml) administered. Conversely, in the TR-DGU cohort, 91.1% patients received pre-hospital crystalloid fluids, with a median volume of 756 ml (750-912 ml) administered. Notably, both cohorts demonstrated a consistent year-on-year decrease in the volume of pre-hospital fluid administered, accompanied by improvements in admission coagulation function and reduced mortality rates. CONCLUSION: Considerable variability exists in pre-hospital fluid resuscitation strategies for blunt trauma patients. Our data suggest a trend towards reduced pre-hospital fluid administration over time. This trend appears to be associated with improved coagulation function and decreased mortality rates. However, we acknowledge that these outcomes are influenced by multiple factors, including other improvements in pre-hospital care over time. Future research should aim to identify which trauma populations may benefit, be harmed, or remain unaffected by different pre-hospital fluid resuscitation strategies.

Intravenous albumin in cardiac and vascular surgery: a systematic review and meta-analysis.

BACKGROUND: Intravenous albumin is commonly utilised in cardiovascular surgery for priming of the cardiopulmonary bypass circuit, volume replacement, or both, although the evidence to support this practice is uncertain. The aim was to compare i.v. albumin with synthetic colloids and crystalloids for paediatric and adult patients undergoing cardiovascular surgery for all-cause mortality and other perioperative outcomes. METHODS: A systematic review and meta-analysis of randomised controlled trials (RCTs) of i.v. albumin compared with synthetic colloids and crystalloids on the primary outcome of all-cause mortality was conducted. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use; subgroups were analysed by age, comparator fluid, and intended use (priming, volume, or both). We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CCRT) from 1946 to November 23, 2022. RESULTS: Of 42 RCTs, mortality was assessed in 15 trials (2711 cardiac surgery patients) and the risk difference was 0.00, 95% confidence interval (CI) -0.01 to 0.01, I2=0%. Among secondary outcomes, i.v. albumin resulted in smaller fluid balance, mean difference -0.55 L, 95% CI -1.06 to -0.4, I2=90% (nine studies, 1975 patients) and higher albumin concentrations, mean difference 7.77 g L-1, 95% CI 3.73-11.8, I2=95% (six studies, 325 patients). CONCLUSIONS: Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids. The lack of improvement in important outcomes with albumin and its higher cost suggests it should be used restrictively. SYSTEMATIC REVIEW PROTOCOL: PROSPERO; CRD42020171876.

Balanced Crystalloids Versus Normal Saline in Kidney Transplant Patients: An Updated Systematic Review, Meta-analysis, and Trial Sequential Analysis.

BACKGROUND: The use of balanced crystalloids over normal saline for perioperative fluid management during kidney transplantation and its benefits on acid-base and electrolyte balance along with its influence on postoperative clinical outcomes remains a topic of controversy. Therefore, we conducted this review to assess the impact of balanced solutions compared to normal saline on outcomes for kidney transplant patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing balanced lower-chloride solutions to normal saline in renal transplant patients. Our main outcome of interest was delayed graft function (DGF). Additionally, we examined acid-base and electrolyte measurements, along with postoperative renal function. We computed relative risk (RR) using the Mantel-Haenszel test for binary outcomes, and mean difference (MD) for continuous data, and applied DerSimonian and Laird random-effects models to address heterogeneity. Furthermore, we performed a trial sequential analysis (TSA) for all outcomes. RESULTS: Twelve RCTs comprising a total of 1668 patients were included; 832 (49.9%) were assigned to receive balanced solutions. Balanced crystalloids reduced the occurrence of DGF compared to normal saline, with RR of 0.82 (95% confidence interval [CI], 0.71-0.94), P = .005; I² = 0%. The occurrence was 25% (194 of 787) in the balanced crystalloids group and 34% (240 of 701) in the normal saline group. Moreover, our TSA supported the primary outcome result and suggests that the sample size was sufficient for our conclusion. End-of-surgery chloride (MD, -8.80 mEq·L -1 ; 95% CI, -13.98 to -3.63 mEq.L -1 ; P < .001), bicarbonate (MD, 2.12 mEq·L -1 ; 95% CI, 1.02-3.21 mEq·L -1 ; P < .001), pH (MD, 0.06; 95% CI, 0.04-0.07; P < .001), and base excess (BE) (MD, 2.41 mEq·L -1 ; 95% CI, 0.88-3.95 mEq·L -1 ; P = .002) significantly favored the balanced crystalloids groups and the end of surgery potassium (MD, -0.17 mEq·L -1 ; 95% CI, -0.36 to 0.02 mEq·L -1 ; P = .07) did not differ between groups. However, creatinine did not differ in the first (MD, -0.06 mg·dL -1 ; 95% CI, -0.38 to 0.26 mg·dL -1 ; P = .71) and seventh (MD, -0.06 mg·dL -1 ; 95% CI, -0.18 to 0.06 mg·dL -1 ; P = .30) postoperative days nor urine output in the first (MD, -1.12 L; 95% CI, -3.67 to 1.43 L; P = .39) and seventh (MD, -0.01 L; 95% CI, -0.45 to 0.42 L; P = .95) postoperative days. CONCLUSIONS: Balanced lower-chloride solutions significantly reduce the occurrence of DGF and provide an improved acid-base and electrolyte control in patients undergoing kidney transplantation.

Sodium bicarbonate Ringer's solution for hemorrhagic shock: A meta-analysis comparing crystalloid solutions.

BACKGROUND: The choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics. OBJECTIVE: To evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions. METHOD: A comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events. RESULT: The meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p = 0.08; I2 = 0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p < 0.0001; I2 = 22%), a mean difference in heart rate of -4.49 (95% CI: -7.55, -1.44; p = 0.004; I2 = 13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: -0.85, 5.47; p = 0.15; I2 = 66%). CONCLUSION: BRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver.

Accelerated lymph flow from infusion of crystalloid fluid during general anesthesia.

BACKGROUND: Kinetic analysis of crystalloid fluid yields a central distribution volume (Vc) of the same size as the expected plasma volume (approximately 3 L) except during general anesthesia during which Vc might be only half as large. The present study examined whether this difference is due to influence of the intravascular albumin balance. METHODS: A population volume kinetic analysis according to a three-compartment model was performed based on retrospective data from 160 infusion experiments during which 1-2.5 L of crystalloid fluid had been infused intravenously over 20-30 min. The plasma dilution based on blood hemoglobin (Hb) and plasma albumin (Alb) was measured on 2,408 occasions and the urine output on 454 occasions. One-third of the infusions were performed on anesthetized patients while two-thirds were given to awake healthy volunteers. RESULTS: The Hb-Alb dilution difference was four times greater during general anesthesia than in the awake state (+ 0.024 ± 0.060 versus - 0.008 ± 0.050; mean ± SD; P < 0.001) which shows that more albumin entered the plasma than was lost by capillary leakage. The Hb-Alb dilution difference correlated strongly and positively with the kinetic parameters governing the rate of fluid transfer through the fast-exchange interstitial fluid compartment (k12 and k21) and inversely with the size of Vc. Simulations suggest that approximately 200 mL of fluid might be translocated from the interstitial space to the plasma despite ongoing fluid administration. CONCLUSIONS: Pronounced plasma volume expansion early during general anesthesia is associated with a positive intravascular albumin balance that is due to accelerated lymphatic flow. This phenomenon probably represents adjustment of the body fluid volumes to anesthesia-induced vasodilatation.

Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis.

BACKGROUND: In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence. METHODS: The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids. RESULTS: The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid. CONCLUSION: Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.

Effect of 5% albumin on endothelial glycocalyx degradation during off-pump coronary artery bypass.

PURPOSE: The integrity of the endothelial glycocalyx (EG), a critical player in vascular homeostasis, reportedly influences the outcomes of critically ill patients. We investigated the effect of 5% albumin, which preserved EG integrity in preclinical studies, vs balanced crystalloid solution on EG degradation in patients undergoing off-pump coronary surgery. METHODS: Patients were randomized to receive either 5% albumin (N = 51) or balanced crystalloid solution (Plasma-Lyte [Baxter Incorporated, Seoul, Republic of Korea]; N = 53) for intravenous volume replacement during surgery (double-blinded). The primary outcome was plasma syndecan-1 concentration, a marker of EG degradation, measured after anesthetic induction (baseline), completion of grafting, and sternal closure. Secondary outcomes were atrial natriuretic peptide (ANP), tumour necrosis factor (TNF)-α, soluble thrombomodulin, and perioperative fluid balance. RESULTS: The mean (standard deviation) fluid requirements were 833 (270) mL and 1,323 (492) mL in the albumin and Plasma-Lyte group, respectively (mean difference, -489 mL; 95% confidence interval [CI], -643 to -335; P < 0.001). Plasma syndecan-1 concentration increased after completion of grafting (median difference, 116 ng·mL-1; 95% CI, 67 to 184; P < 0.001) and sternal closure (median difference, 57 ng·mL-1; 95% CI, 36 to 80; P < 0.001) compared with those at baseline, without any intergroup differences. Atrial natriuretic peptide, TNF-α, and soluble thrombomodulin concentrations were similar between the two groups. The amount of chest tube drainage was greater in the albumin group than that in the Plasma-Lyte group (median difference, 190 mL; 95% CI, 18 to 276; P = 0.03). CONCLUSION: Off-pump coronary surgery was associated with significant EG degradation. Yet, intraoperative fluid therapy with 5% albumin could not ameliorate EG degradation when compared with balanced crystalloid solution. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03699462); first posted 9 October 2018.

RéSUMé: OBJECTIF: L'intégrité du glycocalyx endothélial (GE), un acteur essentiel de l'homéostasie vasculaire, influencerait le devenir des patient·es gravement malades. Nous avons étudié l'effet de l'albumine à 5 %, qui préservait l'intégrité du GE dans les études précliniques, par rapport à une solution cristalloïde équilibrée sur la dégradation du GE chez les patient·es bénéficiant d'une chirurgie coronarienne à cœur battant. MéTHODE: Les patient·es ont été randomisé·es à recevoir soit de l'albumine à 5 % (N = 51) ou de la solution cristalloïde équilibrée (Plasma-Lyte [Baxter Incorporated, Séoul, République de Corée]; N = 53) pour le remplacement du volume intraveineux pendant la chirurgie (en double aveugle). Le critère d'évaluation principal était la concentration plasmatique de syndécan-1, un marqueur de la dégradation du GE, mesurée après l'induction de l'anesthésie (ligne de base), la fin de la greffe et la fermeture du sternum. Les critères d'évaluation secondaires étaient le peptide natriurétique auriculaire (ANP), le facteur de nécrose tumorale (TNF)-α, la thrombomoduline soluble et le bilan hydrique périopératoire. RéSULTATS: Les besoins liquidiens moyens (écart type) étaient de 833 (270) mL et 1323 (492) mL dans les groupes albumine et Plasma-Lyte, respectivement (différence moyenne, −489 mL; intervalle de confiance [IC] à 95 %, −643 à −335; P < 0,001). La concentration plasmatique de syndécan-1 a augmenté après la fin de la greffe (différence médiane, 116 ng·mL−1; IC 95 %, 67 à 184; P < 0,001) et la fermeture du sternum (différence médiane, 57 ng·mL−1; IC 95 %, 36 à 80; P < 0,001) par rapport aux concentrations au départ, sans différences intergroupe. Les concentrations de peptide natriurétique auriculaire, de TNF-α et de thrombomoduline soluble étaient similaires entre les deux groupes. La quantité de drainage du drain thoracique était plus importante dans le groupe albumine que dans le groupe Plasma-Lyte (différence médiane, 190 mL; IC 95 %, 18 à 276; P = 0,03). CONCLUSION: La chirurgie coronarienne à cœur battant a été associée à une dégradation significative du glycocalyx endothélial. Pourtant, la fluidothérapie peropératoire avec 5 % d'albumine n'a pas pu améliorer la dégradation du GE par rapport à une solution cristalloïde équilibrée. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03699462); enregistrée pour la première fois le 9 octobre 2018.

Safety and Efficacy of Albumin for Pump Priming in Cardiac Surgery: A Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of albumin as pump priming fluid in cardiac surgery. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Each study was conducted in a surgical center or intensive care unit. PARTICIPANTS: Adult and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass who received circuit priming fluids. INTERVENTIONS: Extracorporeal circuit priming with either albumin or crystalloid. MEASUREMENTS AND RESULTS: Fourteen eligible randomized controlled trials with 741 patients were included in the present meta-analysis. Albumin prime had lower bleeding (CI -202.20 to -142.88 mL, p < 0.00001) and showed a greater advantage in preserving platelet counts (CI 14.85-21.48 × 103 mm-3, p < 0.00001), maintaining colloid osmotic pressure and sustaining negative fluid balance. No significant differences were found in the remaining study outcomes. CONCLUSIONS: Albumin was shown to be safe and efficacious in extracorporeal circulation perfusion. However, its clinical advantages were not clearly highlighted, as there were no significant differences in the number of deaths, length of hospital stay, or intensive care unit duration. The results should be interpreted cautiously, as most included studies were small in scale, and the total number of participants was limited.

Effect of Urine Output on the Predictive Precision of NephroCheck in On-Pump Cardiac Surgery With Crystalloid Cardioplegia: Insights from the PrevAKI Study.

OBJECTIVES: Previous studies in other settings suggested that urine output (UO) might affect NephroCheck predictive value. We investigated the correlation between NephroCheck and UO in cardiac surgery patients. DESIGN: Post hoc analysis of a multicenter study. SETTING: University hospital. PARTICIPANTS: Patients who underwent cardiac surgery using cardiopulmonary bypass (CPB) and crystalloid cardioplegia. MEASUREMENTS AND MAIN RESULTS: All patients underwent NephroCheck testing 4 hours after CPB discontinuation. The primary outcome was the correlation between UO, NephroCheck results, and acute kidney injury (AKI, defined according to Kidney Disease: Improving Global Outcomes). Of 354 patients, 337 were included. Median NephroCheck values were 0.06 (ng/mL)2/1,000) for the overall population and 0.15 (ng/mL)2/1,000) for patients with moderate to severe AKI. NephroCheck showed a significant inverse correlation with UO (ρ = -0.17; p = 0.002) at the time of measurement. The area under the receiver characteristic curve (AUROC) for NephroCheck was 0.60 (95% confidence interval [CI], 0.54-0.65), whereas for serum creatinine was 0.82 (95% CI, 0.78-0.86; p < 0.001). When limiting the analysis to the prediction of moderate to severe AKI, NephroCheck had a AUROC of 0.82 (95% CI, 0.77 to 0.86; p<0.0001), while creatinine an AUROC of 0.83 (95% CI, 0.79-0.87; p = 0.001). CONCLUSIONS: NephroCheck measured 4 hours after the discontinuation from the CPB predicts moderate to severe AKI. However, a lower threshold may be necessary in patients undergoing cardiac surgery with CPB. Creatinine measured at the same time of the test remains a reliable marker of subsequent development of renal failure.

Assessment of Outcomes in Patients with Heart Failure and End-Stage Kidney Disease after Fluid Resuscitation for Sepsis and Septic Shock.

BACKGROUND: Sepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients. OBJECTIVE: The aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD). METHODS: A retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days. RESULTS: One hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed. CONCLUSIONS: Receipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion.

Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a pilot randomised controlled trial.

BACKGROUND: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA. METHODS: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation. RESULTS: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up. CONCLUSIONS: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED. TRIAL REGISTRATION NUMBER: NCT04926740.

A novel versatile concept of cardioplegia delivery in cardiac surgery: The ReverseTWO cardioplegia circuit system.

Nowadays, the necessity of having a cardioplegia circuit capable of being adapted in order to administer different types of cardioplegia is strategically fundamental, both for the perfusionist and for the cardiac surgeon. This allows to avoid cutting tubes, guarantees sterility and, most of all, limits the number of cardioplegia circuits for the different strategies of cardiac arrest. The novel "ReverseTWO cardioplegia circuit system" is the development of the precedent "Reverse system" where mainly the 4:1 and crystalloid cardioplegia were used, It has the advantage of allowing immediate change of cardioplegia set-up versus four types of cardioplegia technique, when the strategy is unexpectedly changed before the beginning of cardiopulmonary bypass (CPB), is safe and enables the perfusionist to use one single custom pack of cardioplegia. Two pediatric roller pumps are usually used in our centre for cardioplegia administration; they have a standardized calibration (the leading with » inch and the follower with 1/8 inch) and the circuit consequently has two different tube diameters for the two different pumps. The presence in the circuit of two different shunts coupled with two different coloured clamps allows the immediate set-up for different cardioplegia administration techniques utilizing a colour-coding mechanism The aim of this manuscript is to present the new ReverseTWO Circuit. This novel system allows to administer four different cardioplegic solutions (4:1, 1:4, crystalloid, ematic) based on multiple tubes, which can be selectively clamped, identified through a color-coding method. The specificity of this circuit is the great versatility, which leads to numerous advantages, such as reduced risk of perfusion accident and reduced costs related not only to the purchase of different cardioplegia kits but also to the storage. https://youtu.be/ovJBE4ok2Ds.

Changes in temperature in preheated crystalloids at ambient temperatures relevant to a prehospital setting: an experimental simulation study with the application of prehospital treatment of trauma patients suffering from accidental hypothermia.

BACKGROUND: Accidental hypothermia is common in all trauma patients and contributes to the lethal diamond, increasing both morbidity and mortality. In hypotensive shock, fluid resuscitation is recommended using fluids with a temperature of 37-42°, as fluid temperature can decrease the patient's body temperature. In Sweden, virtually all prehospital services use preheated fluids. The aim of the present study was to investigate how the temperature of preheated infusion fluids is affected by the ambient temperatures and flow rates relevant for prehospital emergency care. METHODS: In this experimental simulation study, temperature changes in crystalloids preheated to 39 °C were evaluated. The fluid temperature changes were measured both in the infusion bag and at the patient end of the infusion system. Measurements were conducted in conditions relevant to prehospital emergency care, with ambient temperatures varying between - 4 and 28 °C and flow rates of 1000 ml/h and 6000 ml/h, through an uninsulated infusion set at a length of 175 cm. RESULTS: The flow rate and ambient temperature affected the temperature in the infusion fluid both in the infusion bag and at the patient end of the system. A lower ambient temperature and lower flow rate were both associated with a greater temperature loss in the infusion fluid. CONCLUSION: This study shows that both a high infusion rate and a high ambient temperature are needed if an infusion fluid preheated to 39 °C is to remain above 37 °C when it reaches the patient using a 175-cm-long uninsulated infusion set. It is apparent that the lower the ambient temperature, the higher the flow rate needs to be to limit temperature loss of the fluid.

Transfusion practice in Central Norway - a regional cohort study in patients suffering from major haemorrhage.

BACKGROUND: In patients with major hemorrhage, balanced transfusions and limited crystalloid use is recommended in both civilian and military guidelines. This transfusion strategy is often applied in the non-trauma patient despite lack of supporting data. The aim of this study was to describe the current transfusion practice in patients with major hemorrhage of both traumatic and non-traumatic etiology in Central Norway, and discuss if transfusions are in accordance with appropriate massive transfusion protocols. METHODS: In this retrospective observational cohort study, data from four hospitals in Central Norway was collected from 01.01.2017 to 31.12.2018. All adults (≥18 years) receiving massive transfusion (MT) and alive on admission were included. MT was defined as transfusion of ≥10 units of packed red blood cells (PRBC) within 24 hours, or ≥ 5 units of PRBC during the first 3 hours after admission to hospital. Clinical data was collected from the hospital blood bank registry (ProSang) and electronic patient charts (CareSuite PICIS). Patients undergoing cardiothoracic surgery or extracorporeal membrane oxygenation treatment were excluded. RESULTS: A total of 174 patients were included in the study, of which 85.1% were non-trauma patients. Seventy-six per cent of all patients received plasma:PRBC in a ratio ≥ 1:2 (high ratio) and 59.2% of patients received platelets:PRBC in a ratio ≥ 1:2 (high ratio). 32.2% received a plasma:PRBC-ratio ≥ 1:1, and 23.6% platelet:PRBC-ratio ≥ 1:1. Median fluid infusion of crystalloids in all patients was 5750 mL. Thirty-seven per cent of all patients received tranexamic acid, 53.4% received calcium and fibrinogen concentrate was administered in 9.2%. CONCLUSIONS: Most patients had a non-traumatic etiology. The majority was transfused with high ratios of plasma:PRBC and platelet:PRBC, but not in accordance with the aim of the local protocol (1:1:1). Crystalloids were administered liberally for both trauma and non-trauma patients. There was a lower use of hemostatic adjuvants than recommended in the local transfusion protocol. Awareness to local protocol should be increased.

Usage of mineralocorticoids and isotonic crystalloids in subarachnoid hemorrhage patients in the United States.

BACKGROUND: The usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crystalloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients across the United States are unknown. METHODS: We surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites in 2023, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters from 2010 to 2020 in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20 % of all acute inpatient care in the United States. RESULTS: Although mineralocorticoids are used by 70 % of the NINDS StrokeNet sites, it is used in less than 20 % of the aSAH encounters in the Premier Database. Although saline is ubiquitously used, balanced crystalloids are increasingly used for fluid therapy in aSAH patients. Its use in the NINDS StrokeNet sites and the Premier Healthcare Database is 41 and 45 %, respectively. CONCLUSIONS: The use of mineralocorticoids remains low, and balanced crystalloids are increasingly used as fluid therapy in aSAH patients. The effectiveness of mineralocorticoids and balanced crystalloids in improving outcomes for aSAH patients must be rigorously tested in randomized clinical trials.