Hypovolemia with peripheral edema: What is wrong?

Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1ß, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.

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.

Balanced Crystalloid versus Saline in Adults with Traumatic Brain Injury: Secondary Analysis of a Clinical Trial.

Balanced crystalloids may improve outcomes compared with saline for some critically ill adults. Lower tonicity of balanced crystalloids could worsen cerebral edema in patients with intracranial pathology. The effect of balanced crystalloids versus saline on clinical outcomes in patients with traumatic brain injury (TBI) requires further study. We planned an a priori subgroup analysis of TBI patients enrolled in the pragmatic, cluster-randomized, multiple-crossover Isotonic Solutions and Major Adverse Renal Events Trial (SMART) (ClinicalTrials.gov: NCT02444988, NCT02547779). Primary outcome was 30-day in-hospital mortality. Secondary outcomes included hospital discharge disposition (home, facility, death). Regression models adjusted for pre-specified baseline covariates compared outcomes. TBI patients assigned to balanced crystalloids (n = 588) and saline (n = 569) had similar baseline characteristics including Injury Severity Score 19 (10); mean maximum head/neck Abbreviated Injury Score, 3.4 (1.0). Isotonic crystalloid volume administered between intensive care unit admission and first of hospital discharge or 30 days was 2037 (3470) mL and 1723 (2923) mL in the balanced crystalloids and saline groups, respectively (p = 0.18). During the study period, 94 (16%) and 82 (14%) patients (16%) died in the balanced crystalloid and saline groups, respectively (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.60 to 1.75; p = 0.913). Patients in the balanced crystalloid group were more likely to die or be discharged to another medical facility (aOR 1.38 [1.02-1.86]; p = 0.04). Overall, balanced crystalloids were associated with worse discharge disposition in critically injured patients with TBI compared with saline. The confidence intervals cannot exclude a clinically relevant increase in mortality when balanced crystalloids are used for patients with TBI.

Impact of chloride-rich crystalloids on sepsis-associated community-acquired acute kidney injury recovery in critically ill patients.

BACKGROUND: The use of chloride-rich crystalloids for resuscitation is associated with acute kidney injury (AKI). We aimed to explore the impact of resuscitation with chloride-rich crystalloids compared to balanced crystalloids on kidney function recovery in patients presenting with sepsis-associated community-acquired AKI (SACA-AKI). METHODS: This is a single-center, historical cohort study of the adult intensive care unit (ICU) patients who presented to the emergency department (ED) with  sepsis-associated community-acquired-AKI at the Mayo Clinic, Rochester, MN, from January 2011 to April 2018. We divided the cohort into two groups based on the primary type of crystalloids they received in the ED and the first 48-h of ICU. The first group received primarily normal saline with < 25% balanced solutions, and the second group received at least ≥ 25% balanced crystalloids during the initial volume resuscitation. RESULTS: Among the 732 enrolled patients [mean age: 64 ± 17, males: 461(63%)], 255 (35%) were in the second group and were found to have higher positive fluid balance during the first 48-h of admission compared to the first group [median + 2.3 (IQR: 0.4; 4.5) vs. + 1.1 (IQR: - 0.8; + 2.9) L, p < 0.001]. The second group had a higher rate of kidney function recovery by multivariate logistic regression after adjustments for known recovery risk factors (OR 1.46; 95% CI 1.05-2.04, p = 0.02). CONCLUSIONS: The use of balanced crystalloids during the initial resuscitation is associated with higher odds of kidney function recovery in AKI patients with sepsis-associated community-acquired AKI.

Blood product resuscitation mitigates the effects of aeromedical evacuation after polytrauma.

BACKGROUND: The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight. METHODS: An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes. RESULTS: Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1ß was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR. CONCLUSION: Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.

A Randomized, Multicenter, Open-Label, Blinded End Point, Phase 2, Feasibility, Efficacy, and Safety Trial of Preoperative Microvascular Protection in Patients Undergoing Major Abdominal Surgery.

BACKGROUND: The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary and exploratory outcomes included efficacy and safety. METHODS: We conducted a multicenter, open-label, blinded end point, phase 2, randomized trial. Patients undergoing colorectal, pancreas, or liver surgery were recruited and randomized to receive either intravenous dexamethasone (16 mg) and 20% albumin (100 mL) at induction of anesthesia, then 200 mL of 20% albumin with each subsequent 1000 mL of crystalloid administered (dexamethasone and albumin [Dex-Alb] group), or crystalloid fluid only with no dexamethasone (control group). Feasibility end points included patient recruitment and retention, consent rate, and successful study drug administration. The primary efficacy end point was the measurement of plasma syndecan-1 level on postoperative day (POD) 1, and secondary end points were heparan sulfate levels and inflammatory markers measured at 4 perioperative timepoints. Safety end points included errors in administration of the intervention, hyperglycemia, occurrence of postoperative complications, and patient retention. RESULTS: Seventy-two patients were randomized. All feasibility end points were achievable. There were no statistically significant differences observed in median (interquartile range) syndecan-1 levels on POD 1 (39 ng·mL-1 [20-97] in the Dex-Alb group versus 41 ng·mL-1 [19-84] in the control group; difference in medians -2.1, 95% confidence interval [CI], -13 to 8.6; P = .69). The Dex-Alb group had lower POD 1 heparan sulfate levels (319 ng·mL-1 [161-717] in the Dex-Alb group versus 1422 [670-2430] ng·mL-1 in the control group; difference in medians -1085, 95% CI, -1779 to -391) and C-reactive protein (CRP) levels on POD 1 (48 [29-77] mg·L-1 in the Dex-Alb group versus 85 mg·L-1 [49-133] in the control group; difference in medians -48, 95% CI, -75 to -21). Fewer patients had one or more postoperative complication in the Dex-Alb group than in the control group (6 [17%] vs 18 patients [50%]; odds ratio = 0.2, 95% CI, 0.06-0.6). CONCLUSIONS: Intravenous dexamethasone and albumin administration was feasible but did not reduce syndecan-1 on POD 1 in patients undergoing abdominal surgery. Given the clinically important CIs observed between the groups for heparan sulfate, CRP, and postoperative complications, a larger trial assessing the associations between dexamethasone and albumin administration and these outcomes is warranted.

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

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

Decreased transfusion requirements with use of acute normovolemic hemodilution in open aortic aneurysm repair.

OBJECTIVE: Acute normovolemic hemodilution (ANH) is an operative blood conservation technique involving the removal and storage of patient blood after the induction of anesthesia, with maintenance of normovolemia by crystalloid and/or colloid replacement. Developed and used predominately in cardiac surgery, ANH has been applied to the vascular surgery population. However, data regarding the effects on transfusion requirements in this population are limited. The objective of the present study was to compare the transfusion requirements and coagulopathy for patients who had undergone open abdominal aortic aneurysm repair (oAAAR) using ANH to those for patients who had received only product replacements, as clinically indicated. METHODS: We performed a retrospective review of patients who had undergone elective oAAAR at a quaternary aortic referral center from 2017 to 2019. Those eligible for ANH, with no active cardiac ischemia, no valvular disease, normal left ventricular and right ventricular function, chronic kidney disease stage <3, hematocrit >38%, and a normal coagulation profile were included in the present study. Patient demographics and characteristics and operative variables, including aneurysm extent, clamp site, visceral and renal ischemia time, operative time, and transfusion requirements, were collected. Postoperative morbidity, mortality, and length of stay were analyzed. The patients with and without ANH were matched and compared. Continuous measures were analyzed using Wilcoxon rank sum tests and t tests. RESULTS: During the study period, 209 oAAARs had been performed. Of the 209 patients, 76 had met the inclusion criteria. Of these 76 patients, 27 had undergone ANH and 49 had not. The patients with ANH had required fewer PRBC transfusions intraoperatively (median, 0 U; interquartile range [IQR], 0-1 U; median, 1 U; IQR, 0-2 U; P = .02), at 24 hours (median, 0 U; IQR, 0-1 U; vs median, 1 U; IQR, 0-2 U; P = .008), at 48 hours (median, 0 U; IQR, 0-1 U; vs median, 1 U; IQR, 0-2; P = .007), and throughout the admission (median, 0 U; IQR, 0-1 U; vs median, 2 U; IQR, 0-2 U; P = .011). No difference was found in the number of intraoperative platelet or cryoprecipitate transfusions. At 48 hours, the ANH group had had significantly greater platelet counts (142 ± 35.8 × 103/µL vs 124 ± 37.6 × 103/µL; P = .044), lower partial thromboplastin time, and lower international normalized ratio. No difference in myocardial infarction, return to the operating room, or mortality (one death overall). The ANH patients had a shorter length of stay (7.0 ± 2.7 vs 8.8 ± 4.8 days; P = .041). CONCLUSIONS: The use of ANH during oAAAR resulted in fewer intraoperative and postoperative PRBC transfusions with improved coagulation parameters and a shorter hospital length of stay.

Aggressive crystalloid adversely affects outcomes in a pediatric trauma population.

INTRODUCTION: Crystalloid resuscitation for trauma patients is deleterious, and minimizing crystalloid use is advocated. The purpose of this study was to evaluate the adverse effects of high-volume resuscitation in pediatric blunt trauma patients. METHODS: This study included a retrospective review of 291 patients with blunt trauma from January 2007 to Apr 2018 at the Children's Hospital, Chongqing Medical University. Patients were dichotomized into low and high groups depending on the average dose of crystalloid fluid administration with a cut-off point during the first 24 or 48 h. Propensity score matching was used based on measurable baseline factors to minimize confounding. The associations between crystalloid administration and clinical outcomes were determined according to the corresponding methods. RESULTS: Patients who received larger doses of crystalloids were more likely than the low-volume group to be associated with severe anemia (p = 0.033, p = 0.042, respectively), RBC transfusion (p = 0.016, p = 0.009, respectively) and longer hospital length of stay (p = 0.008, p = 0.002, respectively). In terms of plasma transfusion and oral solid diet, there were marginally significant differences noted in the dichotomized groups at 24 h (p = 0.074), with significant differences at 48 h (p = 0.013). CONCLUSION: Significant unfavorable outcomes were noted following excessive crystalloid resuscitation within the first 48 h among pediatric patients with blunt trauma. Our findings support the notion that excessive fluid resuscitation should be avoided.

Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials.

Importance: Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline. Objective: To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA. Design, Setting, and Participants: This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020. Interventions: Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule. Main Outcomes and Measures: The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion. Results: Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03). Conclusions and Relevance: In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA. Trial Registration: ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.

High crystalloid volumes negate benefit of hemostatic resuscitation in pediatric wartime trauma casualties.

BACKGROUND: Recent data for adult trauma patients suggest improved survival when using hemostatic resuscitation, which includes limiting crystalloids and using closer to 1:1 ratios for both fresh frozen plasma (FFP) and platelets (PLTs) relative to packed red blood cells (PRBCs). Pediatric studies have shown similar but mixed results and often lack measuring crystalloids. We seek to evaluate in-hospital survival based on crystalloid administration and different blood product ratios in pediatric casualties during the recent conflicts. METHODS: We queried the Department of Defense Trauma Registry for all pediatric encounters in Iraq and Afghanistan from January 2007 to January 2016 and included those with at least 40 mL/kg of total blood products administered provided that they received at least 1 U of PRBC. We grouped children as younger (0-7 years) and older (8-17 years). We grouped low versus high ratios for FFP/PRBC (≤1:2 vs. >1:2) and PLT/PRBC (≤1:6 vs. >1.6). We used a threshold of 40 mL/kg to for high versus low crystalloid resuscitation. RESULTS: During this time, there were 3,439 encounters in the registry with 521 (15.1%) that met the inclusion criteria. The median age of casualties that met the inclusion was 10 years (interquartile range, 5-13), most were male (73.5%), with a moderate median injury severity score (17; interquartile range, 13-25). We performed regression modeling with adjustments for mechanism of injury, composite injury severity score, and total blood product volume (mL/kg based), grouping children based on high versus low fluid resuscitation. In the low-volume crystalloid group, we found that higher (>1:2) FFP/PRBC was associated with improved survival (odds ratio [OR], 3.42). However, in the high fluid crystalloid resuscitation group, we found that that higher ratios for PLT/PRBC (>1:6) overall (OR, 0.46) and the FFP/PRBC (>1:2) in younger children (OR, 0.28) was associated with worse survival. The remaining associations were not statistically significant. CONCLUSION: We found an association with survival in massively transfused pediatric trauma patients who received both a high FFP/PRBC ratio and low crystalloid administration. The benefit of this high ratio is negated, in patients receiving high crystalloid volumes, particularly among smaller children. Future studies on hemostatic resuscitation evaluating blood product ratios should also account for crystalloid and colloid administration. LEVEL OF EVIDENCE: Retrospective, comparative, level III.

Crystalloid Administration Is Associated with the Recovery of Pediatric Elective Roux-en-Y Hepaticojejunostomy.

INTRODUCTION: Intraoperative fluid administration is important for postoperative recovery and might be associated with postoperative complications. MATERIALS AND METHODS: This retrospective review included 471 patients who underwent Roux-en-Y hepaticojejunostomy. Patients were separated into two groups based on whether they received low (<15.27 mL/kg/h) or high (>15.27 mL/kg/h) volumes of corrected crystalloid fluids. Propensity score matching was performed to adjust for any potential selection bios for the two groups. In 192 matched patients, clinical outcomes, including postoperative complications and length of hospital stay, were compared. RESULTS: Higher use of diuresis (p = 0.027) was found in the high fluid group. Receiving low volumes of crystalloids was associated with postoperative gastrointestinal functional recovery, reflected by the first defecation (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.31-1.07; p = 0.047) and first bowel movement (OR, 0.56; 95% CI, 0.38-0.98; p = 0.013). However, the occurrence of renal complications did not show significant differences between the groups. A lower postoperative complication rate (OR, 0.54; 95% CI, 0.42-0.94; p = 0.016) was noted in patients with low crystalloids compared with high crystalloids. The total length of hospital stay was longer in patients with high crystalloid fluid (9.21 ± 3.24 days) than patients with low volumes (7.83 ± 2.58 days; p = 0.012). CONCLUSION: Low crystalloid fluid administration was associated with favorable postoperative outcomes.

Aggressive Crystalloid Resuscitation Outcomes in Low-Severity Pediatric Trauma.

BACKGROUND: Trauma is the leading cause of death among children. Studies have found that insufficient intravenous (IV) fluid resuscitation contributes significantly to morbidity and mortality in pediatric trauma. While large-volume resuscitation represents a potential solution, overly aggressive fluid management may complicate hospitalizations and recovery. Through this study, we aim to evaluate the impact of aggressive fluid resuscitation on outcomes in pediatric trauma. MATERIALS AND METHODS: This is a retrospective review utilizing our level I trauma center registry for pediatric patients aged <16 y admitted from 2014 to 2017. Patients transferred from our center within 24 h and those who arrived from outside hospitals were excluded. Patients who received blood product transfusions were excluded. Included patients were divided into two crystalloid groups: <60 mL/kg/24 h and ≥60 mL/kg/24 h. Outcome measures included ICU length-of-stay, length-of-hospitalization, complications, and mortality rate. RESULTS: Study sample included 320 patients (<60 mL/kg/24 h = 219; ≥60 mL/kg/24 h = 101). The ≥60 mL/kg/24 h group was younger (9.95 versus 5.27, P = 0.0001). There were no significant differences in GCS on arrival, injury severity score, Abbreviated Injury Scale, Revised Trauma Scores, traumatic brain injury, and operative intervention between groups. Outcome measures showed there was no significant difference in 30-day readmission rate, complications, or mortality. Large-volume crystalloid resuscitation was associated with longer mean ICU length-of-stay (1.5 d versus 0.8 d, P = 0.004). CONCLUSIONS: In this single-institution retrospective database analysis, large-volume crystalloid resuscitation (≥60 mL/kg) was associated with a significant increase in ICU length-of-stay without survival benefit. More research in the form of randomized trials will help determine the optimal rate for fluid resuscitation in pediatric trauma patients while weighing potential critical care complications.

A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics.

BACKGROUND & AIMS: Blood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output. METHODS: Healthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging. RESULTS: Ten of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index. CONCLUSIONS: A smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid. TRIAL REGISTRATION: The protocol was registered with the European Union Drug Regulating Authorities Clinical Trials Database (https://eudract.ema.europa.eu) (EudraCT No. 2013-003260-32).

Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis.

Background: The optimal resuscitative fluid remains controversial. Objective: To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2 = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2 = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2 = 42%). Conclusion and Relevance: Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.

Major venous injury and large volume crystalloid resuscitation: A limb threatening combination.

INTRODUCTION: Major venous injury (MVI) affecting the lower extremity can result in subsequent amputation. The contribution of intraoperative resuscitation efforts on the need for amputation is not well defined. We hypothesized that intraoperative large volume crystalloid resuscitation (LVCR) increases the risk of amputation after MVI, while massive transfusion (MT) does not. METHODS: We performed a retrospective review of patients with infrarenal MVI from 2005 to 2015 at seven urban level I trauma centers. The outcome of interest was the need for secondary amputation. RESULTS: 478 patients were included. 31 (6.5%) patients with MVI required amputation. LVCR(p < 0.001), combined arterial/venous injury (p = 0.001), and associated fracture (p = 0.001) were significant risk factors for amputation. MT did not significantly increase amputation risk (p = 0.44). Multivariable logistic regression model demonstrated that patients receiving ≥5L LVCR(aOR (95% CI): 9.7 (2.9, 33.0); p < 0.001), with combined arterial/venous injury (aOR (95% CI):3.6 (1.5, 8.5); p = 0.004), and with an associated fracture (aOR (95% CI):3.2 (1.5, 7.1); p = 0.004) were more likely to require amputation. CONCLUSION: Patients with MVI who receive LVCR, have combined arterial/venous injuries and have associated fractures are more likely to require amputation. MT was not associated with delayed amputation.

End-Expiratory Occlusion Test to Predict Fluid Responsiveness Is Not Suitable for Laparotomic Surgery.

BACKGROUND: The end-expiratory occlusion test predicts fluid responsiveness in ventilated intensive care patients; however, its utility in the operating room is questioned. We assessed end-expiratory occlusion test in laparotomic surgery for predicting volume expansion. METHODS: Forty-six patients were included in this study: stage 1 (n = 26) with an end-expiratory occlusion test of 15 seconds, followed by volume expansion, which consisted of 250 mL of colloid over 5 minutes and stage 2 (n = 20) with an end-expiratory occlusion test of 25 seconds followed by volume expansion. The last 10 patients had transdiaphragmatic pressures probed. Patients with an increase in cardiac index >15% after volume expansion were responders. Pulse pressure variation, stroke volume (SV) index, and cardiac index were analyzed. Receiver operating characteristic curves were established for changes in SV and pulse pressure induced by end-expiratory occlusion test and pulse pressure variation using the responders status for volume expansion as outcome. RESULTS: A total of 44 (38%) volume expansions were deemed responders. After end-expiratory occlusion test of 15 seconds, no hemodynamic variables were significantly increased. After end-expiratory occlusion test of 25 seconds, SV index increased in responders (37.1 ± 8.8 mL/m after end-expiratory occlusion test of 25 seconds versus 35.7 ± 8.6 before; P < .0001). End-expiratory occlusion test could not discriminate responders from nonresponders. Only pulse pressure variation had significantly different area under the curve from that expected by chance (0.7 [0.57-0.81]; P = .002 for end-expiratory occlusion test of 15 seconds; and 0.78 [0.64-0.89]; P = .0001 for end-expiratory occlusion test of 25 seconds). After laparotomy, gastric pressure decreased significantly (4 [2.75-5] vs 2 [2-4] cm H2O; P = .0417); no difference was noticed in the transdiaphragmatic gradient. CONCLUSIONS: End-expiratory occlusion test was not reliable to discriminate responders from nonresponders after volume expansion during laparotomic surgery.

Excessive intravenous crystalloid infusion after video-assisted thoracoscopic surgery lobectomy is associated with postoperative pneumonia.

BACKGROUND: Video-assisted thoracoscopic surgery has been widely used in thoracic surgery worldwide. Our goal was to identify the risk factors for postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery lobectomy. METHODS: A retrospective analysis of adult patients undergoing video-assisted thoracoscopic surgery lobectomy between 2016 and 05 and 2017-04 was performed. We used univariate analyses and multivariate analyses to examine risk factors for postoperative pneumonia after lobectomy. RESULTS: The incidence of postoperative pneumonia was 19.7% (n = 143/727). Patients with postoperative pneumonia had a higher postoperative length of stay and total hospital care costs when compared to those without postoperative pneumonia. Multivariate analysis showed that body mass index grading ≥24.0 kg/m2 (vs. <24.0 kg/m2: odds ratio 1.904, 95% confidence interval 1.294-2.802, P = 0.001) and right lung lobe surgery (vs. left lung lobe surgery: odds ratio 1.836, 95% confidence interval 1.216-2.771, P = 0.004) were independent risk factors of postoperative pneumonia. Total intravenous crystalloid infusion grading in the postoperative 24 h ≥ 1500 mL was also identified as the risk factors (vs. 1000 to < 1500 mL: odds ratio 2.060, 95% confidence interval 1.302-3.260, P = 0.002). CONCLUSIONS: Major risk factors for postoperative pneumonia following video-assisted thoracoscopic surgery lobectomy are body mass index grading ≥24.0 kg/m2, right lung lobe surgery and total intravenous crystalloid infusion grading in the postoperative 24 h ≥ 1500 mL.

Why physiology will continue to guide the choice between balanced crystalloids and normal saline: a systematic review and meta-analysis.

BACKGROUND: Crystalloids are the most frequently prescribed drugs in intensive care medicine and emergency medicine. Thus, even small differences in outcome may have major implications, and therefore, the choice between balanced crystalloids versus normal saline continues to be debated. We examined to what extent the currently accrued information size from completed and ongoing trials on the subject allow intensivists and emergency physicians to choose the right fluid for their patients. METHODS: Systematic review and meta-analysis with random effects inverse variance model. Published randomized controlled trials enrolling adult patients to compare balanced crystalloids versus normal saline in the setting of intensive care medicine or emergency medicine were included. The main outcome was mortality at the longest follow-up, and secondary outcomes were moderate to severe acute kidney injury (AKI) and initiation of renal replacement therapy (RRT). Trial sequential analyses (TSA) were performed, and risk of bias and overall quality of evidence were assessed. Additionally, previously published meta-analyses, trial sequential analyses and ongoing large trials were analysed for included studies, required information size calculations and the assumptions underlying those calculations. RESULTS: Nine studies (n = 32,777) were included. Of those, eight had data available on mortality, seven on AKI and six on RRT. Meta-analysis showed no significant differences between balanced crystalloids versus normal saline for mortality (P = 0.33), the incidence of moderate to severe AKI (P = 0.37) or initiation of RRT (P = 0.29). Quality of evidence was low to very low. Analysis of previous meta-analyses and ongoing trials showed large differences in calculated required versus accrued information sizes and assumptions underlying those. TSA revealed the need for extremely large trials based on our realistic and clinically relevant assumptions on relative risk reduction and baseline mortality. CONCLUSIONS: Our meta-analysis could not find significant differences between balanced crystalloids and normal saline on mortality at the longest follow-up, moderate to severe AKI or new RRT. Currently accrued information size is smaller, and the required information size is larger than previously anticipated. Therefore, completed and ongoing trials on the topic may fail to provide adequate guidance for choosing the right crystalloid. Thus, physiology will continue to play an important role for individualizing this choice.