The safety and efficacy of balanced crystalloid vs. normal saline in non-cardiac surgeries - A systematic review and meta-analysis.

OBJECTIVE: Balanced crystalloid and normal saline are routinely used in clinical anesthesia, but their safety and efficacy in non-cardiac surgeries are still unclear. MATERIALS AND METHODS: PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI, from January 1980 to March 2023, were searched. Studies comparing balanced crystalloid (BC) with normal saline (NS) during non-cardiac surgeries were included. The primary outcomes were clinical outcomes (acidosis, renal insufficiency, and mortality), and the secondary outcomes were pH value, Na+, Cl- and creatinine levels, and vasopressor requirement. RESULTS: Forty-three RCTs were included in this meta-analysis. Low evidence revealed that the development of acidosis was lower in the BC group than in the NS group (OR: 0.05, 95% CI: 0.01-0.43, I2=80.8%, p=0.00), and no between-group difference exists in renal insufficiency and mortality. At the end of surgery and on postoperative day 1 (POD 1), the pH value was higher, and the levels of Na+ and Cl- were lower in the BC group. No between-group difference exists in creatinine level and vasopressor requirement. CONCLUSIONS: Perioperative balanced crystalloids can maintain the stability of acid-base and electrolyte balance and reduce acidosis compared with saline, but they cannot reduce postoperative renal insufficiency and mortality.

Exploration of factors affecting hemodynamic stability following pheochromocytoma resection - cohort study.

Purpose: Surgery is the only way to cure pheochromocytoma; however, postoperative hemodynamic instability is one of the main causes of serious complications and even death. This study's findings provide some guidance for improved clinical management. Patients and methods: This study was to investigate the factors leading to postoperative hemodynamic instability in the postoperative pathology indicated pheochromocytoma from May 2016 to May 2022. They were divided into two groups according to whether vasoactive drugs were used for a median number of days or more postoperatively. The factors affecting the postoperative hemodynamics in the perioperative period (preoperative, intraoperative, and postoperative) were then evaluated. Results: The median number of days requiring vasoactive drug support postoperatively was three in 234 patients, while 118 (50.4%) patients required vasoactive drug support for three days or more postoperatively. The results of the multivariate analysis indicated more preoperative colloid use (odds ratio [OR]=1.834, confidence interval [CI]:1.265-2.659, P=0.001), intraoperative use of vasoactive drug (OR=4.174, CI:1.882-9.258, P<0.001), and more postoperative crystalloid solution input per unit of body weight per day (ml/kg/d) (OR=1.087, CI:1.062-1.112, P<0.001) were risk factors for predicting postoperative hemodynamic instability. The optimal cutoff point of postoperative crystalloid use were 42.37 ml/kg/d. Conclusion: Hemodynamic instability is a key issue for consideration in the perioperative period of pheochromocytoma. The amount of preoperative colloid use, the need for intraoperative vasoactive drugs, and postoperative crystalloid solution are risk factors for predicting postoperative hemodynamic instability (registration number: ChiCT2300071166).

How a positive fluid balance develops in acute kidney injury: A binational, observational study.

PURPOSE: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients. METHODS: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy. RESULTS: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001). CONCLUSION: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB. KEY POINTS: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use.

Is crystalloid co-loading necessary to prevent spinal hypotension during elective cesarean delivery? A randomized double-blind trial.

BACKGROUND: Hypotension is common during spinal anesthesia for cesarean delivery. Preventive strategies include fluid loading and phenylephrine. We hypothesized that if prophylactic phenylephrine infusion is used, omission of fluid loading would be non-inferior to fluid co-loading in maintaining cardiac output. We assumed that if there was a difference, the increase in cardiac output would be greater in the no-loading than in the co-loading group. METHODS: Term pregnant women scheduled for elective cesarean delivery were randomized to receive 1 L crystalloid co-loading or maintenance fluids only. Phenylephrine was titrated to maintain blood pressure. Changes in cardiac output following spinal anesthesia were the primary outcome. The study was powered as a non-inferiority trial, allowing the no-loading arm to have a 50% greater change in cardiac output. Heart rate, dose of phenylephrine, occurrence of nausea and vomiting, Apgar scores and neonatal acid base status were secondary outcomes. RESULTS: Data from 63 women were analyzed. In contrast to our hypothesis, there was 33% less increase in cardiac output with no loading (ratio 0.67, 95% CI 0.15 to 1.36), and 60% greater reduction of cardiac output with no loading (ratio 1.6, 95% CI 1.0 to 2.7). Total dose of phenylephrine was higher in the no-loading group. There may be a less favorable neonatal acid base status without volume loading. CONCLUSION: Omission of crystalloid co-loading leads to a decrease in cardiac output which has a potentially unfavorable impact on neonatal acid base status. We conclude that crystalloid co-loading may be useful in the presence of phenylephrine infusion.

Assessing resuscitation in burn patients with varying degrees of liver disease.

We find minimal literature and lack of consensus among burn practitioners over how to resuscitate thermally injured patients with pre-existing liver disease. Our objective was to assess burn severity in patients with a previous history of liver disease. We attempted to stratify resuscitation therapy utilised, using it as an indicator of burn shock severity. We hypothesized that as severity of liver disease increased, more fluid therapy is needed. We retrospectively studied adult patients with a total body surface area (TBSA) of burn greater than or equal to 20% (n = 314). We determined the severity of liver disease by calculating admission Model for End-Stage Liver Disease (MELD) scores and measured resuscitation adequacy via urine output within the first 24 h. We performed stepwise, multivariable linear regression with backward selection to test our hypothesis with α = 0.05 defined a priori. After controlling for important confounders including age, TBSA, baseline serum albumin, total crystalloids, colloids, blood products, diuretics, and steroids given in first 24 h, we found a statistically significant reduction in urine output as MELD score increased (p < 0.000). In our study, severity of liver disease correlated with declining urine output during first 24-hour resuscitation more so than burn size or burn depth. While resuscitation is standardized for all patients, lack of urine output with increased liver disease suggests a new strategy is of benefit. This may involve investigation of alternate markers of adequacy of resuscitation, or developing modified resuscitation protocols for use in patients with liver disease. More investigation is necessary into how resuscitation protocols may best be modified.

Early high-volume resuscitation with crystalloid solution combined with albumin improves survival of critically ill patients: A retrospective analysis from MIMIC-IV database.

BACKGROUND: Volume resuscitation is often required in critically ill patients. However, we have no clear consensus on the choice between crystalloid solution and colloidal solution. This study aimed to explore the effect of albumin administration in massive fluid resuscitation. METHODS: This was a retrospective cohort study based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (2008 and 2019). The prognosis of patients receiving albumin in combination with crystalloids and those receiving crystalloids alone was compared to assess the benefits of albumin in fluid resuscitation. RESULTS: 4426 patients received crystalloids alone (crystalloids group), 692 patients received albumin in combination with crystalloids within the first 24 h of initiation of crystalloids (early albumin combination group), and 382 patients received albumin after the first 24 h (late albumin combination group). Patients in early albumin combination group were more severe than those in Crystalloids group. Nevertheless, we found no statistically significant difference in mortality between the two groups. Multivariate logistic regression analysis using the propensity-score matched cohort showed that the 28-day and 60-day mortality in the early albumin combination group were lower than those in the crystalloids group (odds ratio: 0.64 [95% CI 0.50-0.82; P < 0.001] and 0.71 [95% CI 0.56-0.90; P = 0.004], respectively. Patients in early albumin combination group lived, on average, 1.16 days (95% CI 0.33-2.00; P < 0.01) and 3.3 days (95% CI 1.15-5.44; P < 0.01) longer than the crystalloids group during 28-day follow-up and 60-day follow-up. CONCLUSION: Administration of albumin within 24 h after the initiation of crystalloids was associated with a lower mortality and a longer restricted mean survival time during 28-day follow-up and 60-day follow-up compared with crystalloid infusion alone. However, administration of albumin 24 h after the initiation of crystalloids was not associated with better prognosis compared to crystalloid infusion alone.

Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery.

BACKGROUND: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. METHODS: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. RESULTS: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229). CONCLUSIONS: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit.

Accuracy of cumulative volumes of fluid challenge to assess fluid responsiveness in critically ill patients with acute circulatory failure: a pharmacodynamic approach.

BACKGROUND: The relationship between the dose (volume of fluid) and the effect (increase of stroke volume [SV]) has been poorly described. We hypothesised that the analysis of the dynamic response of SV during fluid challenge (FC) helps to determine the optimal volume of FC, along with its diagnostic accuracy parameters for fluid responsiveness. METHODS: A prospective observational study was conducted in critically ill patients with circulatory failure. Patients monitored with oesophageal Doppler and assigned to an FC of 500 ml of crystalloid were included. The areas under the curve (AUC) and 95% confidence intervals (CI95) of the receiver operating characteristic curves for cumulative volumes from 50 to 450 ml were determined for fluid responsiveness (SV increase ≥15% from baseline) along with other parameters of diagnostic accuracy. In the pharmacodynamic analysis, dose-effect and dose-response models were constructed, with determination of median and 90% effective dose (ED50 and ED90). RESULTS: Forty-five patients were included. The AUC increased with cumulative volumes of FC up to 250 ml (AUC250 0.93 [CI95: 0.85-1.00]), followed by a plateau above 0.95 of AUC. The optimal volume was 250 ml, associated with a specificity of 0.89 [CI95: 0.78-1.00], a sensitivity of 0.92 [CI95: 0.69-1.00], and a threshold of 9.6% increase in SV. The ED50 was 156 [CI95: 136-177] ml and the ED90 was 312 [CI95: 269-352] ml. CONCLUSIONS: A volume of FC of 250 ml with a threshold of 9.6% increase in SV showed the highest accuracy in detecting fluid responsiveness in critically ill patients with shock. CLINICAL TRIAL REGISTRATION: .

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.

Balanced crystalloids versus saline in critically ill patients: The PRISMA study of a meta-analysis.

OBJECTIVE: To compare the safety of balanced crystalloids and saline among critically ill patients in intensive care unit (ICU). METHODS: The Medline, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to May 17, 2020 in order to identify randomized controlled trials which evaluated the safety of balanced crystalloids and saline in critically ill patients. The primary outcome was major adverse kidney events within 30 days (MAKE30). The second outcomes included 30-day mortality, ICU mortality, In-hospital mortality, ICU length of stay, hospital length of stay, creatinine highest before discharge (mg/dl) and needs for renal replacement therapy (RRT). RESULTS: A total of nine randomized controlled trials involving 19,578 critical ill patients fulfilled the inclusion criteria. The outcomes of this meta-analysis showed that balanced crystalloids treatment shared the same risk of MAKE30 with saline treatment among critical ill patients [RR = 0.95; 95%CI, 0.88 to 1.01; Z = 1.64 (P = .102)]. The clinical mortality which included 30-day mortality [RR = 0.92; 95%CI, 0.85 to 1.01; Z = 1.78 (P = .075)], ICU mortality [RR = 0.92; 95%CI, 0.83 to 1.02; Z = 1.67 (P = .094)] and In-hospital mortality [RR = 0.93; 95%CI, 0.71 to 1.21; Z = 0.55 (P = .585)] were similar between balanced crystalloids treatment and saline treatment among critical ill patients. Patients who received balanced crystalloids treatment or saline treatment needed the same length of ICU stay [WMD = 0.00; 95%CI, -0.09 to 0.10; Z = 0.09 (P = .932)] and hospital stay [WMD = 0.59; 95%CI, -0.33 to 1.51; Z = 1.26 (P = .209)]. Critical ill patients who received balanced crystalloids treatment or saline treatment had the same level of creatinine highest before discharge [WMD = 0.01; 95%CI, -0.02 to 0.04; Z = 0.76 (P = .446)] and needs for RRT [RR = 1.04; 95%CI, 0.75 to 1.43; Z = 0.21 (P = .830)]. Similar results were obtained in subgroups of trials stratified according to the age of patients (children or adults). CONCLUSIONS: When compared with saline, balanced crystalloids could not reduce the risk of MAKE30, 30-day mortality, ICU mortality and in-hospital mortality, could not reduce the length of ICU stay, length of hospital stay, the level of creatinine highest before discharge and the needs for RRT among critical ill children and adults. Therefore, it was still too early for balanced crystalloids to replace normal saline among critical ill patients.

Acute intensive care unit resuscitation of severely injured trauma patients: Do we need a new strategy?

BACKGROUND: Unlike recent advances in blood product resuscitation, intravenous crystalloid (IVF) use after intensive care unit (ICU) admission in hemorrhagic shock has received less attention and current recommendations are based on limited evidence. To address this knowledge gap, we aimed to determine associations between IVF administration during acute ICU resuscitation and outcomes. We hypothesized that larger IVF volumes are associated with worse outcomes. METHODS: We linked our trauma registry with electronic health record data (2012-2015) to identify adults with an initial lactate level of ≥4 mmol/L and documented lactate normalization (≤2 mmol/L), excluding those with isolated head Abbreviated Injury Scale score ≥3. We focused on the period from ICU admission to lactate normalization, analyzing duration, volume of IVF, and proportion of volume as 1-L boluses. We used linear regression to determine associations with ICU length of stay and duration of mechanical ventilation in survivors, and logistic regression to identify associations with acute kidney injury and home discharge while adjusting for important covariates. RESULTS: We included 337 subjects. Median time to lactate normalization was 15 hours (interquartile range, 7-25 hours), and median IVF volume was 3.7 L (interquartile range, 1.5-6.4 L). The fourfold difference between the upper and lower quartiles of both duration and volume remained after stratifying by injury severity. Hourly volumes tapered over time but persistently aggregated at 0.5 and 1 L, with 167 subjects receiving at least one 0.5-L bolus for 6 hours after ICU admission. Administration of larger volumes was associated with longer ICU length of stay and duration of mechanical ventilation, as well as acute kidney injury. CONCLUSION: There is substantial variation in volume administered during acute ICU resuscitation, both absolutely and temporally, despite accounting for injury severity. Administration of larger volumes during acute ICU resuscitation is associated with worse outcomes. There is an opportunity to improve outcomes by further investigating and standardizing this important phase of care. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Initial fluid resuscitation (30 mL/kg) in patients with septic shock: More or less?

OBJECTIVES: The 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is limited evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock. METHODS: This was a multicenter prospective observational study of adult patients with septic shock who were admitted to four intensive care units (ICUs) in a total of three Jiangsu Province teaching hospitals over a 3-year span from May 8, 2018, to June 15, 2021. Each enrolled patients with septic shock was categorized into the low-volume (below 20 mL/kg fluid), medium-volume (20-30 mL/kg fluid) or high-volume (above 30 mL/kg fluid) fluid group according to the initial infusion dose given for fluid resuscitation. Various demographic attributes and other variables were collected from medical records. Logistic regression and Kaplan-Meier curve analysis were used to determine the relationship between initial fluid resuscitation doses and patient outcomes. MEASUREMENTS AND MAIN RESULTS: A total of 302 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the high-volume group (48.3%) and lowest in the medium-volume group (26.3%, P < 0.05). Patients who completed 30 mL/kg initial fluid resuscitation in the first 1-2 h had the lowest 28-day mortality rate (22.8%, P < 0.05). Logistic regression showed that a medium initial fluid volume dose was an independent protective factor, with the odds ratio (OR) indicating significantly decreased mortality (OR, 0.507; 95% confidence interval, 0.310-0.828; P = 0.007; P < 0.05). A Kaplan-Meier curve stratified by initial fluid resuscitation dose was constructed for the probability of 28-day mortality. The medium-volume fluid group showed a significantly lower 28-day mortality rate than the high-volume group or the low-volume group (log-rank test, P = 0.0016). CONCLUSION: In septic shock patients, an initial fluid resuscitation rate of 20-30 mL/kg within the first hour may be associated with reduced 28-day mortality; however, this result needs to be confirmed by further high-quality randomized controlled clinical trials. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674.

Rational Fluid Resuscitation in Sepsis for the Hospitalist: A Narrative Review.

Administration of fluid is a cornerstone of supportive care for sepsis. Current guidelines suggest a protocolized approach to fluid resuscitation in sepsis despite a lack of strong physiological or clinical evidence to support it. Both initial and ongoing fluid resuscitation requires careful consideration, as fluid overload has been shown to be associated with increased risk for mortality. Initial fluid resuscitation should favor balanced crystalloids over isotonic saline, as the former is associated with decreased risk of renal dysfunction. Traditionally selected resuscitation targets, such as lactate elevation, are fraught with limitations. For developing or established septic shock, a focused hemodynamic assessment is needed to determine if fluid is likely to be beneficial. When initial fluid therapy is unable to achieve the blood pressure goal, initiation of early vasopressors and admission to intensive care should be favored over repetitive administration of fluid.

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.

Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED: systematic review with narrative synthesis.

BACKGROUND: Based on the 2018 update of the Surviving Sepsis Campaign, the Committee for Quality Improvement of the NHSs of England recommended the instigation of the elements of the 'Sepsis-6 bundle' within 1 hour to adult patients screened positive for sepsis. This bundle includes a bolus infusion of 30 mL/kg crystalloids in the ED. Besides the UK, both in the USA and Australia, compliance with similar 1-hour targets became an important quality indicator. However, the supporting evidence may neither be contemporaneous nor necessarily valid for emergency medicine settings. METHOD: A systematic review was designed and registered at PROSPERO to assess available emergency medicine/prehospital evidence published between 2012 and 2020, investigating the clinical benefits associated with a bolus infusion of a minimum 30 mL/kg crystalloids within 1 hour to adult patients screened positive for sepsis. Due to the small number of papers that addressed this volume of fluids in 1 hour, we expanded the search to include studies looking at 1-6 hours. RESULTS: Seven full-text articles were identified, which investigated various aspects of the fluid resuscitation in adult sepsis. However, none answered completely to the original research question aimed to determine either the effect of time-to-crystalloids or the optimal fluid volume of resuscitation. Our findings demonstrated that in the USA/UK/Australia/Canada, adult ED septic patients receive 23-43 mL/kg of crystalloids during the first 6 hours of resuscitation without significant differences either in mortality or in adverse effects. CONCLUSION: This systematic review did not find high-quality evidence supporting the administration of 30 mL/kg crystalloid bolus to adult septic patients within 1 hour of presentation in the ED. Future research must investigate both the benefits and the potential harms of the recommended intervention.

Lactate as a mediator of prehospital plasma mortality reduction in hemorrhagic shock.

BACKGROUND: Prehospital plasma transfusion in trauma reduces mortality. However, the underlying mechanism remains unclear. Reduction in shock severity may play a role. Lactate correlates with physiologic shock severity and mortality after injury. Our objective was to determine if prehospital plasma reduces lactate and if this contributes to the mortality benefit of plasma. METHODS: Patients in the Prehospital Air Medical Plasma trial in the upper quartile of injury severity (Injury Severity Score, >30) were included to capture severe shock. Trial patients were randomized to prehospital plasma or standard care resuscitation (crystalloid ± packed red blood cells). Regression determined the associations between admission lactate, 30-day mortality, and plasma while adjusting for demographics, prehospital crystalloid, time, mechanism, and injury characteristics. Causal mediation analysis determined what proportion of the effect of plasma on mortality is mediated by lactate reduction. RESULTS: A total of 125 patients were included. The plasma group had a lower adjusted admission lactate than standard of care group (coefficient, -1.64; 95% confidence interval [CI], -2.96 to -0.31; p = 0.02). Plasma was associated with lower odds of 30-day mortality (odds ratio [OR], 0.27; 95% CI, 0.08-0.90; p = 0.03). When adding lactate to this model, the effect of plasma on 30-day mortality was no longer significant (OR, 0.36; 95% CI, 0.07-1.88; p = 0.23), while lactate was associated with mortality (OR, 1.74 per 1 mmol/L increase; 95% CI, 1.10-2.73; p = 0.01). Causal mediation demonstrated 35.1% of the total effect of plasma on 30-day mortality was mediated by the reduction in lactate among plasma patients. CONCLUSION: Prehospital plasma is associated with reduced 30-day mortality and lactate in severely injured patients. More than one third of the effect of plasma on mortality is mediated by a reduction in lactate. Thus, reducing the severity of hemorrhagic shock appears to be one mechanism of prehospital plasma benefit. Further study should elucidate other mechanisms and if a dose response exists. LEVEL OF EVIDENCE: Therapeutic, level II.

Hemodynamic Parameters in the Assessment of Fluid Status in a Porcine Hemorrhage and Resuscitation Model.

BACKGROUND: Measuring fluid status during intraoperative hemorrhage is challenging, but detection and quantification of fluid overload is far more difficult. Using a porcine model of hemorrhage and over-resuscitation, it is hypothesized that centrally obtained hemodynamic parameters will predict volume status more accurately than peripherally obtained vital signs. METHODS: Eight anesthetized female pigs were hemorrhaged at 30 ml/min to a blood loss of 400 ml. After each 100 ml of hemorrhage, vital signs (heart rate, systolic blood pressure, mean arterial pressure, diastolic blood pressure, pulse pressure, pulse pressure variation) and centrally obtained hemodynamic parameters (mean pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output) were obtained. Blood volume was restored, and the pigs were over-resuscitated with 2,500 ml of crystalloid, collecting parameters after each 500-ml bolus. Hemorrhage and resuscitation phases were analyzed separately to determine differences among parameters over the range of volume. Conformity of parameters during hemorrhage or over-resuscitation was assessed. RESULTS: During the course of hemorrhage, changes from baseline euvolemia were observed in vital signs (systolic blood pressure, diastolic blood pressure, and mean arterial pressure) after 100 ml of blood loss. Central hemodynamic parameters (mean pulmonary artery pressure and pulmonary capillary wedge pressure) were changed after 200 ml of blood loss, and central venous pressure after 300 ml of blood loss. During the course of resuscitative volume overload, changes were observed from baseline euvolemia in mean pulmonary artery pressure and central venous pressure after 500-ml resuscitation, in pulmonary capillary wedge pressure after 1,000-ml resuscitation, and cardiac output after 2,500-ml resuscitation. In contrast to hemorrhage, vital sign parameters did not change during over-resuscitation. The strongest linear correlation was observed with pulmonary capillary wedge pressure in both hemorrhage (r2 = 0.99) and volume overload (r2 = 0.98). CONCLUSIONS: Pulmonary capillary wedge pressure is the most accurate parameter to track both hemorrhage and over-resuscitation, demonstrating the unmet clinical need for a less invasive pulmonary capillary wedge pressure equivalent.

Higher Crystalloid Volume During Initial Pediatric Trauma Resuscitation is Associated With Mortality.

BACKGROUND: Historically, aggressive fluid resuscitation has been a cornerstone of management of hemorrhagic shock in pediatrics. Adult data suggest this strategy may be harmful. We sought to determine whether aggressive fluid resuscitation within the first hour of presentation to the emergency department in pediatric patients with trauma is associated with worse clinical outcomes. MATERIALS AND METHODS: We performed a retrospective cohort study from 2012 to 2017 at a single pediatric level 1 trauma center. We defined three patient cohorts: ≤ 20 cc/kg (reference), 20-40 (20.01 to 39.99) cc/kg, and ≥40 cc/kg of intravenous fluid (IVF) given in the first in-hospital hour. Covariates included age, injury severity score, shock index (adjusted for age), and mechanism of injury and were adjusted for with multivariable regression. The primary outcome was in-hospital mortality. RESULTS: A total of 1479 consecutive injured children were eligible for inclusion. One hundred ninety-four patients were excluded for missing IVF data, aged ≥16 y, having primary burns, or arriving pulseless. A total of 1285 patients met inclusion criteria (mean age 8.1 ± 5.5 y, male 64.5%). Higher rates of IVF administration were associated with mortality for both the 20-40 cc/kg (adjusted odds ratio (aOR) 2.96; 95% confidence interval (CI) 1.02-8.55; P = 0.045) and ≥40 cc/kg groups (aOR 6.26; 95% CI 1.79-21.83; P = 0.004). The ≥40 cc/kg group was associated with increased pediatric intensive care unit length of stay (aOR 2.20; 95% CI: 1.05-4.61; P = 0.036) and increased need for mechanical ventilation (aOR 3.79; 95% CI 1.62-8.87; P = 0.002). CONCLUSIONS: Greater than one 20 cc/kg IVF bolus in the first emergency department hour was associated with mortality with a dose-response relationship, even after adjusting for injury severity and initial hemodynamics. These results encourage further investigation into initial resuscitation strategies for injured children.