Efficacy of past, present, and future fluid strategies in an improved large animal model of non-compressible intra-abdominal hemorrhage.

BACKGROUND: Noncompressible hemorrhage is a leading cause of potentially survivable combat death, with the vast majority of such deaths occurring in the out-of-hospital environment. While large animal models of this process are important for device and therapeutic development, clinical practice has changed over time and past models must follow suit. Developed in conjunction with regulatory feedback, this study presents a modernized, out-of-hospital, noncompressible hemorrhage model, in conjunction with a randomized study of past, present, and future fluid options following a hypotensive resuscitation protocol consistent with current clinical practice. METHODS: We performed a randomized controlled experiment comparing three fluid resuscitation options in Yorkshire swine. Baseline data from animals of same size from previous experiments were analyzed (n = 70), and mean systolic blood pressure was determined, with a permissive hypotension resuscitation target defined as a 25% decrease from normal (67 mm Hg). After animal preparation, a grade IV to V liver laceration was induced. Animals bled freely for a 10-minute "time-to-responder" period, after which resuscitation occurred with randomized fluid in boluses to the goal target: 6% hetastarch in lactated electrolyte injection (HEX), normal saline (NS), or fresh whole blood (FWB). Animals were monitored for a total simulated "delay to definitive care" period of 2 hours postinjury. RESULTS: At the end of the 2-hour study period, 8.3% (1 of 12 swine) of the HEX group, 50% (6 of 12 swine) of the NS group, and 75% (9 of 12 swine) of the FWB had survived (p = 0.006), with Holm-Sidak pairwise comparisons showing a significant difference between HEX and FWB and (p = 0.005). Fresh whole blood had significantly higher systemic vascular resistance and hemoglobin levels compared with other groups (p = 0.003 and p = 0.001, respectively). CONCLUSION: Survival data support the movement away from HEX toward NS and, preferably, FWB in clinical practice and translational animal modeling. The presented model allows for future research including basic science, as well as translational studies of novel diagnostics, therapeutics, and devices.

Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies. DATA SOURCES: A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. STUDY SELECTION AND DATA EXTRACTION: All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews. DATA SYNTHESIS: A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03-19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51-3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55-5.00) and 1.39 (95% CI, 1.15-1.69) for cumulative fluid balance. Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75-2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81-7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39-1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30-5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03-1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11-1.28) per liter increase in positive fluid balance. CONCLUSIONS: This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.

Impact of intraoperative goal-directed fluid therapy on major morbidity and mortality after transthoracic oesophagectomy: a multicentre, randomised controlled trial.

BACKGROUND: Transthoracic oesophagectomy is associated with major morbidity and mortality, which may be reduced by goal-directed therapy (GDT). The aim of this multicentre, RCT was to evaluate the impact of intraoperative GDT on major morbidity and mortality in patients undergoing transthoracic oesophagectomy. METHODS: Adult patients undergoing transthoracic oesophagectomy were randomised to receive either minimally invasive intraoperative GDT (stroke volume variation <8%, plus systolic BP maintained >90 mm Hg by pressors as necessary) or haemodynamic management left to the discretion of attending senior anaesthetists (control group; systolic BP >90 mm Hg alone). The primary outcome was the incidence of death or major complications (reoperation for bleeding, anastomotic leakage, pneumonia, reintubation, >48 h ventilation). A Cox proportional hazard model was used to examine whether the effects of GDT on morbidity and mortality were independent of other potential confounders. RESULTS: A total of 232 patients (80.6% male; age range: 36-83 yr) were randomised to either GDT (n=115) or to the control group (n=117). After surgery, major morbidity and mortality were less frequent in 22/115 (19.1%) subjects randomised to GDT, compared with 41/117 (35.0%) subjects assigned to the control group {absolute risk reduction: 15.9% (95% confidence interval [CI]: 4.7-27.2%); P=0.006}. GDT was also associated with fewer episodes of atrial fibrillation (odds ratio [OR]: 0.18 [95% CI: 0.05-0.65]), respiratory failure (OR: 0.27 [95% CI: 0.09-0.83]), use of mini-tracheotomy (OR: 0.29 [95% CI: 0.10-0.81]), and readmission to ICU (OR: 0.09 [95% CI: 0.01-0.67]). GDT was independently associated with morbidity and mortality (hazard ratio: 0.51 [95% CI: 0.30-0.87]; P=0.013). CONCLUSIONS: Intraoperative GDT may reduce major morbidity and mortality, and shorten hospital stay, after transthoracic oesophagectomy. CLINICAL TRIAL REGISTRATION: UMIN000018705.

Left Ventricular End-Diastolic Pressure Versus Urine Flow Rate-Guided Hydration in Preventing Contrast-Associated Acute Kidney Injury.

OBJECTIVES: This study compared left ventricular end-diastolic pressure (LVEDP)-guided and urine flow rate (UFR)-guided hydration. BACKGROUND: Tailored hydration regimens improve the prevention of contrast-associated acute kidney injury (CA-AKI). METHODS: Between July 15, 2015, and June 6, 2019, patients at high risk for CA-AKI scheduled for coronary and peripheral procedures were randomized to 2 groups: 1) normal saline infusion rate adjusted according to the LVEDP (LVEDP-guided group); and 2) hydration controlled by the RenalGuard System in order to reach UFR ≥300 ml/h (UFR-guided group). The primary endpoint was the composite of CA-AKI (i.e., serum creatinine increase ≥25% or ≥0.5 mg/dl at 48 h) and acute pulmonary edema (PE). Major adverse events (all-cause death, renal failure requiring dialysis, PE, and sustained kidney injury) at 1 month were assessed. RESULTS: The primary endpoint occurred in 20 of 351 (5.7%) patients in the UFR-guided group and in 36 of 351 (10.3%) patients in the LVEDP-guided group (relative risk [RR]: 0.560; 95% confidence interval [CI]: 0.390 to 0.790; p = 0.036). CA-AKI and PE rates in the UFR-guided group and LVEDP-guided group were 5.7% and 10.0% (RR: 0.570; 95% CI: 0.300 to 0.960; p = 0.048), and, respectively, 0.3% and 2.0% (RR: 0.070; 95% CI: 0.020 to 1.160; p = 0.069). Three patients in the UFR-guided group experienced complications related to the Foley catheter. Hypokalemia rate was 6.2% in the UFR-guided group and 2.3% in the LVEDP-guided group (p = 0.013). The 1-month major adverse events rate was 7.1% in the UFR-guided group and 12.0% in the LVEDP-guided group (p = 0.030). CONCLUSIONS: The study demonstrates that UFR-guided hydration is superior to LVEDP-guided hydration to prevent the composite of CA-AKI and PE.

Effects of intravenous hydration on risk of contrast induced nephropathy and in-hospital mortality in STEMI patients undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of intravenous hydration at the time of primary percutaneous intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains unclear. Guidelines are vague, supported by low level evidence, and hydration is used less often than other clinical settings.To perform a systematic review and meta-analysis of all randomized controlled trials assessing intravenous hydration compared with non-hydration for prevention of contrast induced nephropathy (CIN) and In-hospital mortality in patients with STEMI undergoing primary PCI. METHODS: Medline, EMBASE and the Cochrane Register were searched to September 2018. Included studies reported the incidence of CIN, In-hospital mortality, requirement for dialysis and heart failure. Relative risks with 95% confidence intervals (CIs) for individual trials were pooled using a random effects model. RESULTS: Three moderate quality trials were identified including 1074 patients. Overall, compared with no hydration, intravenous hydration significantly reduced the incidence of CIN by 42% (RR 0.58; 95% CI: 0.45 to 0.74, p < 0.001). The estimated effects upon all-cause mortality (RR 0.56; 95% CI: 0.30 to 1.02, p = 0.057) and the requirement for dialysis (RR 0.52, 95% CI 0.14-1.88, p = 0.462) were not statistically significant. The outcome of heart failure was not consistently reported. CONCLUSIONS: Intravenous hydration likely reduces the incidence of CIN in patients with STEMI undergoing primary PCI. However, for key clinical outcomes such as mortality, heart failure and dialysis the effect estimates were imprecise. Further high quality studies are needed to clarify the appropriate volume of fluid and effects on outcomes.

The impact of intraoperative fluid management during laparoscopic donor nephrectomy on donor and recipient outcomes.

BACKGROUND: Intraoperative fluid management during laparoscopic donor nephrectomy (LDN) may have a significant effect on donor and recipient outcomes. We sought to quantify variability in fluid management and investigate its impact on donor and recipient outcomes. METHODS: A retrospective review of patients who underwent LDN from July 2011 to January 2016 with paired kidney recipients at a single center was performed. Patients were divided into tertiles of intraoperative fluid management (standard, high, and aggressive). Donor and recipient demographics, intraoperative data, and postoperative outcomes were analyzed. RESULTS: Overall, 413 paired kidney donors and recipients were identified. Intraoperative fluid management (mL/h) was highly variable with no correlation to donor weight (kg) (R = 0.017). The aggressive fluid management group had significantly lower recipient creatinine levels on postoperative day 1. However, no significant differences were noted in creatinine levels out to 6 months between groups. No significant differences were noted in recipient postoperative complications, graft loss, and death. There was a significant increase (P < 0.01) in the number of total donor complications in the aggressive fluid management group. CONCLUSIONS: Aggressive fluid management during LDN does not improve recipient outcomes and may worsen donor outcomes compared to standard fluid management.

Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis

ABSTRACT BACKGROUND: This study aimed to compare the effects on mortality of albumin and crystalloid, used for fluid resuscitation among adult patients with septic shock, through conducting a meta-analysis and trial sequential analysis (TSA). DESIGN AND SETTING: Meta-analysis and TSA conducted at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. METHODS: Data were collected from several major databases including MEDLINE, EMBASE, Clinical Trials.gov and Cochrane Central Register of Controlled Trials. Studies that compared the effects of albumin therapy versus crystalloid therapy on mortality among adult septic shock patients were eligible for inclusion in the analyses. The study name, year of publication, country of the trial, albumin concentration, type of crystalloid and all reported mortalities at different follow-up endpoints were extracted. RESULTS: Compared with crystalloid, albumin did not decrease all-cause mortality at the final follow-up. However, in TSA, the required information size was not achieved in all groups, which means that the effect size was not definitive and further RCTs are needed to confirm or deny these findings CONCLUSIONS: Compared with crystalloid solutions, albumin was unable to decrease all-cause mortality. However, TSA indicated that these results could be false-negative. Additional randomized controlled trials are needed to clarify this discrepancy.

Colloids versus crystalloids for fluid resuscitation in critically ill people.

BACKGROUND: Critically ill people may lose fluid because of serious conditions, infections (e.g. sepsis), trauma, or burns, and need additional fluids urgently to prevent dehydration or kidney failure. Colloid or crystalloid solutions may be used for this purpose. Crystalloids have small molecules, are cheap, easy to use, and provide immediate fluid resuscitation, but may increase oedema. Colloids have larger molecules, cost more, and may provide swifter volume expansion in the intravascular space, but may induce allergic reactions, blood clotting disorders, and kidney failure. This is an update of a Cochrane Review last published in 2013. OBJECTIVES: To assess the effect of using colloids versus crystalloids in critically ill people requiring fluid volume replacement on mortality, need for blood transfusion or renal replacement therapy (RRT), and adverse events (specifically: allergic reactions, itching, rashes). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two other databases on 23 February 2018. We also searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of critically ill people who required fluid volume replacement in hospital or emergency out-of-hospital settings. Participants had trauma, burns, or medical conditions such as sepsis. We excluded neonates, elective surgery and caesarean section. We compared a colloid (suspended in any crystalloid solution) versus a crystalloid (isotonic or hypertonic). DATA COLLECTION AND ANALYSIS: Independently, two review authors assessed studies for inclusion, extracted data, assessed risk of bias, and synthesised findings. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 69 studies (65 RCTs, 4 quasi-RCTs) with 30,020 participants. Twenty-eight studied starch solutions, 20 dextrans, seven gelatins, and 22 albumin or fresh frozen plasma (FFP); each type of colloid was compared to crystalloids.Participants had a range of conditions typical of critical illness. Ten studies were in out-of-hospital settings. We noted risk of selection bias in some studies, and, as most studies were not prospectively registered, risk of selective outcome reporting. Fourteen studies included participants in the crystalloid group who received or may have received colloids, which might have influenced results.We compared four types of colloid (i.e. starches; dextrans; gelatins; and albumin or FFP) versus crystalloids.Starches versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using starches or crystalloids in mortality at: end of follow-up (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.86 to 1.09; 11,177 participants; 24 studies); within 90 days (RR 1.01, 95% CI 0.90 to 1.14; 10,415 participants; 15 studies); or within 30 days (RR 0.99, 95% CI 0.90 to 1.09; 10,135 participants; 11 studies).We found moderate-certainty evidence that starches probably slightly increase the need for blood transfusion (RR 1.19, 95% CI 1.02 to 1.39; 1917 participants; 8 studies), and RRT (RR 1.30, 95% CI 1.14 to 1.48; 8527 participants; 9 studies). Very low-certainty evidence means we are uncertain whether either fluid affected adverse events: we found little or no difference in allergic reactions (RR 2.59, 95% CI 0.27 to 24.91; 7757 participants; 3 studies), fewer incidences of itching with crystalloids (RR 1.38, 95% CI 1.05 to 1.82; 6946 participants; 2 studies), and fewer incidences of rashes with crystalloids (RR 1.61, 95% CI 0.90 to 2.89; 7007 participants; 2 studies).Dextrans versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using dextrans or crystalloids in mortality at: end of follow-up (RR 0.99, 95% CI 0.88 to 1.11; 4736 participants; 19 studies); or within 90 days or 30 days (RR 0.99, 95% CI 0.87 to 1.12; 3353 participants; 10 studies). We are uncertain whether dextrans or crystalloids reduce the need for blood transfusion, as we found little or no difference in blood transfusions (RR 0.92, 95% CI 0.77 to 1.10; 1272 participants, 3 studies; very low-certainty evidence). We found little or no difference in allergic reactions (RR 6.00, 95% CI 0.25 to 144.93; 739 participants; 4 studies; very low-certainty evidence). No studies measured RRT.Gelatins versus crystalloidsWe found low-certainty evidence that there may be little or no difference between gelatins or crystalloids in mortality: at end of follow-up (RR 0.89, 95% CI 0.74 to 1.08; 1698 participants; 6 studies); within 90 days (RR 0.89, 95% CI 0.73 to 1.09; 1388 participants; 1 study); or within 30 days (RR 0.92, 95% CI 0.74 to 1.16; 1388 participants; 1 study). Evidence for blood transfusion was very low certainty (3 studies), with a low event rate or data not reported by intervention. Data for RRT were not reported separately for gelatins (1 study). We found little or no difference between groups in allergic reactions (very low-certainty evidence).Albumin or FFP versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using albumin or FFP or using crystalloids in mortality at: end of follow-up (RR 0.98, 95% CI 0.92 to 1.06; 13,047 participants; 20 studies); within 90 days (RR 0.98, 95% CI 0.92 to 1.04; 12,492 participants; 10 studies); or within 30 days (RR 0.99, 95% CI 0.93 to 1.06; 12,506 participants; 10 studies). We are uncertain whether either fluid type reduces need for blood transfusion (RR 1.31, 95% CI 0.95 to 1.80; 290 participants; 3 studies; very low-certainty evidence). Using albumin or FFP versus crystalloids may make little or no difference to the need for RRT (RR 1.11, 95% CI 0.96 to 1.27; 3028 participants; 2 studies; very low-certainty evidence), or in allergic reactions (RR 0.75, 95% CI 0.17 to 3.33; 2097 participants, 1 study; very low-certainty evidence). AUTHORS' CONCLUSIONS: Using starches, dextrans, albumin or FFP (moderate-certainty evidence), or gelatins (low-certainty evidence), versus crystalloids probably makes little or no difference to mortality. Starches probably slightly increase the need for blood transfusion and RRT (moderate-certainty evidence), and albumin or FFP may make little or no difference to the need for renal replacement therapy (low-certainty evidence). Evidence for blood transfusions for dextrans, and albumin or FFP, is uncertain. Similarly, evidence for adverse events is uncertain. Certainty of evidence may improve with inclusion of three ongoing studies and seven studies awaiting classification, in future updates.

Early Fluid Overload Is Associated with an Increased Risk of Nonrelapse Mortality after Ex Vivo CD34-Selected Allogeneic Hematopoietic Cell Transplantation.

In a recently published and validated definition of fluid overload (FO), grade ≥ 2 FO was significantly associated with an increased risk of nonrelapse mortality (NRM) after unmodified and haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using calcineurin inhibitor (CNI)-based graft-versus-host disease (GVHD) prophylaxis. We evaluated the effect of FO on outcomes in 169 patients undergoing myeloablative-conditioned ex vivo CD34+ selected allo-HCT using the same grading scale. Thirty patients (17.8%) had grade ≥ 2 FO within the 30 days after ex vivo CD34+ selected allo-HCT with a median onset at day 11 (range, -8 to 28). Age ≥ 55 years (odds ratio, 3.43; P = .005) and chemotherapy-based conditioning (odds ratio, 3.89; P = .007) were associated with an increased risk of grade ≥ 2 FO. Patients with early grade ≥ 2 FO had a significantly higher NRM when compared with patients with grade < 2 FO (24.1% versus 3.6% at day 100, P = .01). The HCT-specific comorbidity index (HCT-CI) ≥ 3, FEV1 < 80, adjusted DLco < 80, and HLA mismatch were associated with an increased risk of NRM, whereas total body irradiation-based conditioning was associated with a reduced risk of NRM. In a multivariate analysis grade ≥ 2 FO was associated with increased NRM after adjusting for HCT-CI and HLA match (hazard ratio, 2.3; P = .014). There was a trend toward inferior relapse-free survival in patients with grade ≥ 2 FO compared with patients with grade < 2 FO, 62% versus 72% at 1 year (P = .07), and a trend toward inferior overall survival, 69% versus 79% at 1 year (P = 0.06), respectively. Our findings show that FO should be routinely assessed to identify patients at risk for NRM. Despite a CNI-free allo-HCT platform, regimen-related tissue and endothelial injury leads to FO in susceptible patients. FO is a highly relevant post-HCT toxicity that requires further inquiry.

Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures.

BACKGROUND: Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal saline, that feature an electrolyte composition that differs from that of physiological plasma. Buffered fluids have a theoretical advantage of containing a substrate that acts to maintain the body's acid-base status - typically a bicarbonate or a bicarbonate precursor such as maleate, gluconate, lactate, or acetate. Buffered fluids also provide additional electrolytes, including potassium, magnesium, and calcium, more closely matching the electrolyte balance of plasma. The putative benefits of buffered fluids have been compared with those of non-buffered fluids in the context of clinical studies conducted during the perioperative period. This review was published in 2012, and was updated in 2017. OBJECTIVES: To review effects of perioperative intravenous administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance, or both, on clinical outcomes in adults undergoing all types of surgery. SEARCH METHODS: We electronically searched the Clinicaltrials.gov major trials registry, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6) in the Cochrane Library, MEDLINE (1966 to June 2016), Embase (1980 to June 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2016). We handsearched conference abstracts and, when possible, contacted leaders in the field. We reran the search in May 2017. We added one potential new study of interest to the list of 'Studies awaiting classification' and will incorporate this trial into formal review findings when we prepare the review update. SELECTION CRITERIA: Only randomized controlled trials that compared buffered versus non-buffered intravenous fluids for surgical patients were eligible for inclusion. We excluded other forms of comparison such as crystalloids versus colloids and colloids versus different colloids. DATA COLLECTION AND ANALYSIS: Two review authors screened references for eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, in collaboration with a third review author. We contacted trial authors to request additional information when appropriate. We presented pooled estimates for dichotomous outcomes as odds ratios (ORs) and for continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We analysed data via Review Manager 5.3 using fixed-effect models, and when heterogeneity was high (I² > 40%), we used random-effects models. MAIN RESULTS: This review includes, in total, 19 publications of 18 randomized controlled trials with a total of 1096 participants. We incorporated five of those 19 studies (330 participants) after the June 2016 update. Outcome measures in the included studies were thematically similar, covering perioperative electrolyte status, renal function, and acid-base status; however, we found significant clinical and statistical heterogeneity among the included studies. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Trial authors variably reported outcome data at disparate time points and with heterogeneous patient groups. Consequently, many outcome measures are reported in small group sizes, reducing overall confidence in effect size, despite relatively low inherent bias in the included studies. Several studies reported orphan outcome measures. We did not include in the results of this review one large, ongoing study of saline versus Ringer's solution.We found insufficient evidence on effects of fluid therapies on mortality and postoperative organ dysfunction (defined as renal insufficiency leading to renal replacement therapy); confidence intervals were wide and included both clinically relevant benefit and harm: mortality (Peto OR 1.85, 95% CI 0.37 to 9.33; I² = 0%; 3 trials, 6 deaths, 276 participants; low-quality evidence); renal insufficiency (OR 0.82, 95% CI 0.34 to 1.98; I² = 0%; 4 trials, 22 events, 276 participants; low-quality evidence).We noted several metabolic differences, including a difference in postoperative pH measured at end of surgery of 0.05 units - lower in the non-buffered fluid group (12 studies with a total of 720 participants; 95% CI 0.04 to 0.07; I² = 61%). However, this difference was not maintained on postoperative day one. We rated the quality of evidence for this outcome as moderate. We observed a higher postoperative serum chloride level immediately after operation, with use of non-buffered fluids reported in 10 studies with a total of 530 participants (MD 6.77 mmol/L, 95% CI 3.38 to 10.17), and this difference persisted until day one postoperatively (five studies with a total of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). We rated the quality of evidence for this outcome as moderate. AUTHORS' CONCLUSIONS: Current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery. Benefits of buffered fluid were measurable in biochemical terms, particularly a significant reduction in postoperative hyperchloraemia and metabolic acidosis. Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Larger studies are needed to assess these relevant clinical outcomes.

Current management of spontaneous intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) is the most devastating and disabling type of stroke. Uncontrolled hypertension (HTN) is the most common cause of spontaneous ICH. Recent advances in neuroimaging, organised stroke care, dedicated Neuro-ICUs, medical and surgical management have improved the management of ICH. Early airway protection, control of malignant HTN, urgent reversal of coagulopathy and surgical intervention may increase the chance of survival for patients with severe ICH. Intensive lowering of systolic blood pressure to <140 mm Hg is proven safe by two recent randomised trials. Transfusion of platelets in patients on antiplatelet therapy is not indicated unless the patient is scheduled for surgical evacuation of haematoma. In patients with small haematoma without significant mass effect, there is no indication for routine use of mannitol or hypertonic saline (HTS). However, for patients with large ICH (volume > 30 cbic centmetre) or symptomatic perihaematoma oedema, it may be beneficial to keep serum sodium level at 140-150 mEq/L for 7-10 days to minimise oedema expansion and mass effect. Mannitol and HTS can be used emergently for worsening cerebral oedema, elevated intracranial pressure (ICP) or pending herniation. HTS should be administered via central line as continuous infusion (3%) or bolus (23.4%). Ventriculostomy is indicated for patients with severe intraventricular haemorrhage, hydrocephalus or elevated ICP. Patients with large cerebellar or temporal ICH may benefit from emergent haematoma evacuation. It is important to start intermittent pneumatic compression devices at the time of admission and subcutaneous unfractionated heparin in stable patients within 48 hours of admission for prophylaxis of venous thromboembolism. There is no benefit for seizure prophylaxis or aggressive management of fever or hyperglycaemia. Early aggressive comprehensive care may improve survival and functional recovery.

Colloids in Cardiac Surgery-Friend or Foe?

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

Saline versus balanced crystalloids for intravenous fluid therapy in the emergency department: study protocol for a cluster-randomized, multiple-crossover trial.

BACKGROUND: Prior studies in critically ill patients suggest the supra-physiologic chloride concentration of 0.9% ("normal") saline may be associated with higher risk of renal failure and death compared to physiologically balanced crystalloids. However, the comparative effects of 0.9% saline and balanced fluids are largely unexamined among patients outside the intensive care unit, who represent the vast majority of patients treated with intravenous fluids. METHODS/DESIGN: This study, entitled Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED), is a pragmatic, cluster, multiple-crossover trial at a single institution evaluating clinical outcomes of adults treated with 0.9% saline versus balanced crystalloids for intravenous fluid resuscitation in the emergency department. All adults treated in the study emergency department receiving at least 500 mL of isotonic crystalloid solution during usual clinical care and subsequently hospitalized outside the intensive care unit are included. Treatment allocation of 0.9% saline versus balanced crystalloids is assigned by calendar month, with study patients treated during the same month assigned to the same fluid type. The first month (January 2016) was randomly assigned to balanced crystalloids, with each subsequent month alternating between 0.9% saline and balanced crystalloids. For balanced crystalloid treatment, clinicians can choose either Lactated Ringer's or Plasma-Lyte A©. The study period is set at 16 months, which will result in an anticipated estimated sample size of 15,000 patients. The primary outcome is hospital-free days to day 28, defined as the number of days alive and out of the hospital from the index emergency department visit until 28 days later. Major secondary outcomes include proportion of patients who develop acute kidney injury by creatinine measurements; major adverse kidney events by hospital discharge or day 30 (MAKE30), which is a composite outcome of death, new renal replacement therapy, and persistent creatinine elevation >200% of baseline; and in-hospital mortality. DISCUSSION: This ongoing pragmatic trial will provide the most comprehensive evaluation to date of clinical outcomes associated with 0.9% saline compared to physiologically balanced fluids in patients outside the intensive care unit. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02614040 . Registered on 18 November 2015.

Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study.

BACKGROUND: Acute Kidney injury (AKI) is common and increases mortality in the intensive care unit (ICU). We carried out this study to explore whether fluid overload is an independent risk factor for AKI. METHODS: Single-center prospective, observational study. Consecutively admitted, ICU patients were followed for development of AKI. Intravenous fluid volumes, daily fluid balances were measured, hourly urine volumes, daily creatinine levels were recorded. RESULTS: Three hundred thirty nine patients were included; AKI developed in 141 (41.6%) patients; RISK in 27 (8%) patients; INJURY in 25 (7%); FAILURE in 89 (26%) by the RIFLE criteria. Fluid balance was significantly higher in patients with AKI; 1755 ± 2189 v/s 924 ± 1846 ml, p < 0.001 on ICU day 1. On multivariate regression analysis, a net fluid balance in first 24 h of ICU admission, OR 1.02 (95% CI 1.01,1.03 p = 0.003), percentage of fluid accumulation adjusted for body weight OR1.009 (95% CI 1.001,1.017, p = 0.02), fluid balance in first 24 h of ICU admission with serum creatinine adjusted for fluid balance, OR 1.024 (95% CI 1.012,1,035, p = 0.005), Age, OR 1.02 95% CI 1.01,1.03, p < 0.001, CHF, OR 3.1 (95% CI 1.16,8.32, p = 0.023), vasopressor requirement on ICU day one, OR 1.9 (95% CI 1.13,3.19, p = 0.014) and Colistin OR 2.3 (95% CI 1.3, 4.02, p < 0.001) were significant predictors of AKI. There was no significant association between fluid type; Chloride-liberal, Chloride-restrictive, and AKI. CONCLUSIONS: Fluid overload is an independent risk factor for AKI.

Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study.

OBJECTIVE: To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis. STUDY DESIGN: We performed matched analyses using data from 12 529 patients <18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay. RESULTS: The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P < .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group. CONCLUSIONS: Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids.

[No improved survival rate in severely injured patients by prehospital intubation : A retrospective data analysis and matched-pair analysis]. / Kein verbessertes Überleben bei schwerstverletzten Patienten durch die präklinische Intubation : Eine retrospektive Datenanalyse mit Matched-pair-Analyse.

BACKGROUND: Training programs for the treatment of trauma patients generally recommend establishing a secure airway if the patient presents with a Glasgow coma scale (GCS) score of less than 9; however, the evidence for its effectiveness is rather sparse. This study analyzed the effect of preclinical intubation on mortality of patients with a GCS <9 in an emergency medical situation. METHODS: This retrospective analysis included patients who were primarily admitted to a German level 1 trauma center between 2002 and 2012 with an injury severity score (ISS) ≥ 16, a GCS < 9 and primary transport from the site of the accident. Data were collected from the trauma registry of the German Society for Trauma Surgery and from hospital records. A total of 455 patients were included and a matched-pair analysis of 62 patients was conducted. RESULTS: Both analytical methods showed no significant reduction in mortality rate after prehospital intubation. In the retrospective analysis intubated patients presented with a significantly lower systolic blood pressure on admission, received a higher amount of fluid volume at all phases of treatment and arrived at the hospital after a prolonged rescue time. In the matched-pair analysis, intubated patients also received a higher amount of fluid volume and showed better peripheral oxygen saturation on admission. No further differences between the groups could be found. CONCLUSION: It appears that preclinical intubation in trauma patients with a GCS < 9 does not result in a better outcome. The preclinical intubation resulted in a reduced systolic blood pressure on arrival at hospital, a prolonged preclinical rescue time and a greater amount of infused fluid volume.

Prevention of Contrast-Induced Nephropathy by Central Venous Pressure-Guided Fluid Administration in Chronic Kidney Disease and Congestive Heart Failure Patients.

OBJECTIVES: This study aimed to explore the hemodynamic index-guided hydration method for patients with congestive heart failure (CHF) and chronic kidney disease (CKD) to reduce the risk of contrast-induced nephropathy (CIN) and at the same time to avoid the acute heart failure. BACKGROUND: Patients at moderate or high risk for CIN should receive sufficient hydration before contrast application. METHODS: This prospective, randomized, double-blind, comparative clinical trial enrolled 264 consecutive patients with CKD and CHF undergoing coronary procedures. These patients were randomly assigned to either central venous pressure (CVP)-guided hydration group (n = 132) or the standard hydration group (n = 132). In the CVP-guided group, the hydration infusion rate was dynamically adjusted according to CVP level every hour. CIN was defined as an absolute increase in serum creatinine (SCr) >0.5 mg/dl (44.2 µmol/l) or a relative increase >25% compared with baseline SCr. RESULTS: Baseline characteristics were well-matched between the 2 groups. The total mean volume of isotonic saline administered in the CVP-guided hydration group was significantly higher than the control group (1,827 ± 497 ml vs. 1,202 ± 247 ml; p < 0.001). CIN occurred less frequently in CVP-guided hydration group than the control group (15.9% vs. 29.5%; p = 0.006). The incidences of acute heart failure during the hydration did not differ between the 2 groups (3.8% vs. 3.0%; p = 0.500). CONCLUSIONS: CVP-guided fluid administration can safely and effectively reduce the risk of CIN in patients with CKD and CHF. (Central Venous Pressure Guided Hydration Prevention for Contrast-Induced Nephropathy; NCT02405377).

Restrictive versus Standard Fluid Regimen in Elective Minilaparotomy Abdominal Aortic Repair-Prospective Randomized Controlled Trial.

Objective Elective minilaparotomy abdominal aortic aneurysm (AAA) repair is associated with a significant number of complications involving respiratory, cardiovascular, gastrointestinal, and central nervous systems, with mortality ranging up to 5%. In our study, we tested the hypothesis that intra- and postoperative intravenous restrictive fluid regimen reduces postoperative morbidity and mortality, and improves the outcome of minilaparotomy AAA repair. Methods From March 2009 to July 2013, 60 patients operated due to AAA were included in a prospective randomized controlled trial (RCT). About the administration of fluid during the operation and in the early postoperative period, all the patients were randomized into two groups: the group of standard fluid administration (S-group, 30 patients) and the group of reduced fluid administration (R-group, 30 patients). The verification of the treatment success was measured by the length of intensive care unit (ICU) stay, duration of hospitalization after the procedure, as well as the number and type of postoperative complications and mortality. This prospective RCT was registered in a publicly accessible database ClinicalTrials.gov with unique Identifier ID: NTC01939652. Results Total fluid administration and administration of blood products were significantly lower in R-group as compared with S-group (2,445.5 mL vs. 3308.7 mL, p = 0.004). Though the number of nonlethal complications was significantly lower in R-group (2 vs. 9 patients, p = 0.042), the difference in lethal complications remained nonsignificant (0 vs. 1 patient, p = ns). The average ICU stay (1.2 vs. 1.97 days, p = 0.003) and duration of postoperative hospital stay (4.33 vs. 6.20 days, p = 0.035 for R-group and S-group, respectively) were found to be significantly shorter in R-group. Conclusion Intra- and postoperative restrictive intravenous fluid regimen in patients undergoing minilaparotomy AAA repair significantly reduces postoperative morbidity, and shortens ICU and overall hospital stay. Even though incidence of lethal complication was lower in R-group, the difference did not reach statistical significance. Therefore, we may assume that this study was probably underpowered to estimate the differences in mortality between R- and S-groups. Further multicentric, sufficiently powered RCTs are needed to confirm these findings and to clarify effect of restrictive fluid management on mortality.

Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial.

BACKGROUND: Inappropriate fluid therapy during surgery is associated with significant morbidity and mortality. Few studies have examined the effects of particular types of fluids (crystalloid or colloid solutions) in surgical patients, especially with the goal of hemodynamic optimization. Isotonic saline is the most commonly used fluid worldwide but may be associated with potential nephrotoxicity. Hydroxyethyl starch (HES) solutions are widely used in surgical patients as a component of goal-directed fluid optimization strategies, but several large multicenter studies have suggested increased rates of acute kidney injury and adverse events with the use of HES in ICU patients. Despite what may be inferred from physiological studies, the benefit and harm of 0.9 % saline and HES during hemodynamic therapy have not been clearly established in surgical patients. METHODS/DESIGN: The FLASH trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 826 patients with moderate-to-high risk of postoperative complications to receive 6 % HES 130/0.4 or 0.9 % saline during individualized goal-directed fluid optimization. The primary outcome measure is a composite of death or major postoperative complications within 14 days following surgery. The sample size will allow the detection of a 10 % absolute between-group difference in the primary outcome measure with a type 1 error rate of 5 % and power of 95 %, assuming a 5 % mortality rate and 20 % morbidity (thus 25 % for the composite endpoint). DISCUSSION: The FLASH trial may provide important data on the efficacy and safety of commonly used fluid solutions and could have a significant impact on future treatment of surgical patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02502773 . Registered 16 June 2015.

Effect of the amount of intraoperative fluid administration on postoperative pulmonary complications following anatomic lung resections.

OBJECTIVE: Excessive fluid administration during lung resections is a risk for pulmonary injury. We analyzed the effect of intraoperative fluids on postoperative pulmonary complications (PCs). METHODS: Patients who underwent anatomic pulmonary resections during 2012 to 2013 were included. Age, weight, pulmonary function data, smoking (pack-years), the infusion rate and the total amount of intraoperative fluids (including crystalloid, colloid, and blood products), duration of anesthesia, hospital stay, PCs, and mortality were recorded. PCs were defined as acute respiratory distress syndrome, need for intubation, bronchoscopy, atelectasis, pneumonia, prolonged air leak, and failure to expand. Univariate analyses and multivariate logistic regression were performed. A Lowess curve was drawn for intraoperative fluid threshold. RESULTS: In 139 patients, types of resections were segmentectomy-lobectomy (n = 69; extended n = 37; video-assisted thoracoscopic surgery n = 19) and pneumonectomy (n = 9; extended n = 5). One hundred sixty-one PCs were observed in 76 patients (acute respiratory distress syndrome [n = 5], need for intubation [n = 9], atelectasis [n = 60], need for bronchoscopy [n = 19], pneumonia [n = 26], prolonged air leak [n = 19], and failure to expand [n = 23]). Overall mortality was 4.3% (6 out of 139 patients). Mean hospital stay was 8.5 ± 4.8 days. Univariate analyses showed that smoking, intraoperative total amount of fluids, crystalloids, blood products, and infusion rate as well as total amount of crystalloids and infusion rate during the postoperative first 48 hours were significant for PCs (P = .033, P < .0001, P = .001, P = .03, P < .0001, P = .002, and P < .0001, respectively). In multivariate logistic regression analysis intraoperative infusion rate (P < .0001) and smoking were significant (P = .023). An infusion rate of 6 mL/kg/h was found to be the threshold. CONCLUSIONS: The occurrence of postoperative PCs is seen more frequently if the intraoperative infusion rate of fluids exceeds 6 mL/kg/h.