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Goal-directed therapy (GDT) encompasses guidance of intravenous (IV) fluid and vasopressor/inotropic therapy by cardiac output or similar parameters to help in early recognition and management of high-risk cardiac surgical patients. With the aim of establishing the utility of perioperative GDT using robust clinical and biochemical outcomes, we conducted the present study. This multicenter randomized controlled study included 130 patients of either sex, with European system for cardiac operative risk evaluation ≥3 undergoing coronary artery bypass grafting on cardiopulmonary bypass. The patients were randomly divided into the control and GDT group. All the participants received standardized care; arterial pressure monitored through radial artery, central venous pressure (CVP) through a triple lumen in the right internal jugular vein, electrocardiogram, oxygen saturation, temperature, urine output per hour, and frequent arterial blood gas (ABG) analysis. In addition, cardiac index (CI) monitoring using FloTrac™ and continuous central venous oxygen saturation (ScVO2) using PreSep™ were used in patients in the GDT group. Our aim was to maintain the CI at 2.5-4.2 L/min/m2, stroke volume index 30-65 ml/beat/m2, systemic vascular resistance index 1500-2500 dynes/s/cm5/m2, oxygen delivery index 450-600 ml/min/m2, continuous ScVO2 >70%, and stroke volume variation <10%; in addition to the control group parameters such as CVP 6-8 mmHg, mean arterial pressure 90-105 mmHg, normal ABG values, oxygen saturation, hematocrit value >30%, and urine output >1 ml/kg/h. The aims were achieved by altering the administration of IV fluids and doses of inotropes or vasodilators. The data of sixty patients in each group were analyzed in view of ten exclusions. The average duration of ventilation (19.89 ± 3.96 vs. 18.05 ± 4.53 h, P = 0.025), hospital stay (7.94 ± 1.64 vs. 7.17 ± 1.93 days, P = 0.025), and Intensive Care Unit (ICU) stay (3.74 ± 0.59 vs. 3.41 ± 0.75 days, P = 0.012) was significantly less in the GDT group, compared to the control group. The extra volume added and the number of inotropic dose adjustments were significantly more in the GDT group. The two groups did not differ in duration of inotropic use, mortality, and other complications. The perioperative continuation of GDT affected the early decline in the lactate levels after 6 h in ICU, whereas the control group demonstrated a settling lactate only after 12 h. Similarly, the GDT group had significantly lower levels of brain natriuretic peptide, neutrophil gelatinase-associated lipocalin levels as compared to the control. The study clearly depicts the advantage of GDT for a favorable postoperative outcome in high-risk cardiac surgical patients.

Because of its life‐saving benefits, perioperative IV fluid therapy remains a cornerstone of medical treatment. However, it also induces sustained edemagenic stress. The resulting persistent interstitial edema—excessive fluid accumulation in the interstitium—significantly delays recovery and worsens patient outcomes. Therefore, to gain a detailed understanding of the lymphatic functional consequences of perioperative fluid therapy, this study aimed to test the hypothesis that perioperative IV fluid therapy compromises lymphatic pump function within 3 days after major surgery. Following a midline laparotomy, animals received IV fluid therapy over 48 h during recovery (FLTP). Three days post‐surgery, mesenteric lymphatic vessels from FLTP and sham surgery (CTRL) animals were isolated, and lymphatic pump function was assessed in vitro. The transmural pressure‐pump flow and circumferential length‐wall tension relationships of FLTP vessels were altered—contraction frequency and normalized pump flow and active and passive wall tensions were significantly lower than CTRL. In vessels from another group of animals with surgically produced mesenteric venous hypertension to induce sustained edemagenic stress, only the pressure‐pump flow relationship was altered similarly to FLTP. These results demonstrate the detrimental effects of perioperative fluid therapy on lymphatic pumping, which is essential for restoring interstitial fluid pressure and resolving edema and inflammation.

Background: Although goal-directed fluid therapy (GDFT) is associated with reduced morbidity and length of stay (LOS) in the hospital after major surgery, it has not been widely studied in ovarian cancer cytoreductive surgery (CRS). The primary objective of the study was post-operative LOS. Methods: In this double-blind, randomised controlled trial, ovarian cancer patients undergoing elective CRS were randomised to receive either GDFT or restrictive fluid therapy after pre-randomisation stratification for primary debulking surgery or interval debulking surgery. The primary objective was to measure post-operative LOS in the hospital. Secondary outcome measures were the cost of surgical treatment episode and post-operative morbidity assessed by post-operative morbidity survey (POMS) on the 1st, 3rd, 5th, and 7th post-operative day and at discharge. Clavien-Dindo (CD) classification was used to assess the 30-day morbidity/mortality rate. Results: Median LOS was 7 days (interquartile range (IQR): 5-10; P = 0.282) in both groups. Median POMS at day 3 was 3 (IQR: 2-5) in the GDFT and 4 (IQR: 2.25-2.75) in the control groups (P = 0.625). The cost of treatment was INR 310907 (IQR: INR 211,856-427,490) in the GDFT group and INR 342,468 (IQR: INR 270,179-454,122) in the control group (P = 0.100). Grade 3-5 CD morbidity was 7 (12%) in GDFT and 9 (16%) in the control group (P = 0.790). Conclusion: GDFT did not confer significant benefit over restrictive fluid therapy in ovarian cancer CRS regarding hospital LOS.

Background Appropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients’ hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid). Results The metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%, p value = 0.23 and 54.8% vs. 39.8%; p value = 0.09, respectively]. Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = − 0.10 (− 0.14, − 0.07); Chi 2  = 30.97; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = − 0.016 (− 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal ( p value = 0.52) nor cardiovascular ( p value = 0.86) or pulmonary ( p value = 0.14) or neurological ( p value = 0.44) or infective ( p value = 0.12) complications. Conclusions Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality. Trial Registration CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866

Abstract Rationale Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy. Objectives To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes. Methods Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock. Measurements and Main Results We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3. Conclusions In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.

Background： Early goal-directed therapy （EGDT） has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients. Methods： A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients＇ characteristics were compared before treatment （TO）, immediately after EGDT （T 1 ）, and 24 h after EGDT （T2）. This study is registered at ClinicalTrials.org, NCT02060773. Results： Twenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients： therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate （ICG-PDR） and 15-min retention rate （Rl 5） at TO （ 11.9 ±5.0%/min and 20.0 ±13.2%）, T1 （ 11.4 ± 5.1%/min and 23.6 ± 14.9%）, and T2 （ 11.0 ±4.5%/rain and 23.7 ± 15.3%） （all P 〉 0.05）. Both of the alterations of ICG-PDR and R l 5 showed no differences at TO, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected （P 〉 0.05）.

Purpose To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Methods Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. Results From 2395 initially eligible abstracts, five randomised clinical trials ( n  = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2 % [495/2134] versus control: 22.4 % [582/2601]; pooled OR 1.01 [95 % CI 0.88–1.16], P  = 0.9, with heterogeneity [ I 2  = 57 %; P  = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies ( n  = 4063) also showed no difference [pooled OR 0.99 (95 % CI 0.86–1.15), P  = 0.93] with no heterogeneity ( I 2  = 0.0 %; P  = 0.97). EGDT increased vasopressor use (OR 1.25 [95 % CI 1.10–1.41]; P  < 0.001) and ICU admission [OR 2.19 (95 % CI 1.82–2.65); P  < 0.001]. Including six non-ED randomised trials increased heterogeneity ( I 2  = 71 %; P  < 0.001) but did not change overall results [pooled OR 0.94 (95 % CI 0.82 to 1.07); P  = 0.33]. Conclusion EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

Abstract Rationale It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome. Objectives To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit (ICU) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. Methods Patients were randomly allocated to two groups. In the lactate group, treatment was guided by lactate levels with the objective to decrease lactate by 20% or more per 2 hours for the initial 8 hours of ICU stay. In the control group, the treatment team had no knowledge of lactate levels (except for the admission value) during this period. The primary outcome measure was hospital mortality. Measurements and Main Results The lactate group received more fluids and vasodilators. However, there were no significant differences in lactate levels between the groups. In the intention-to-treat population (348 patients), hospital mortality in the control group was 43.5% (77/177) compared with 33.9% (58/171) in the lactate group (P = 0.067). When adjusted for predefined risk factors, hospital mortality was lower in the lactate group (hazard ratio, 0.61; 95% confidence interval, 0.43–0.87; P = 0.006). In the lactate group, Sequential Organ Failure Assessment scores were lower between 9 and 72 hours, inotropes could be stopped earlier, and patients could be weaned from mechanical ventilation and discharged from the ICU earlier. Conclusions In patients with hyperlactatemia on ICU admission, lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors. As this was consistent with important secondary endpoints, this study suggests that initial lactate monitoring has clinical benefit. Clinical trial registered with www.clinicaltrials.gov (NCT00270673).

Abstract The use of pulmonary artery catheters has diminished, so that other technologies are emerging. Central venous oxygen saturation measurement (ScvO2) as a surrogate for mixed venous oxygen saturation measurement (Sv−O2) is simple and clinically accessible. To maximize the clinical utility of ScvO2 (or Sv−O2) measurement, it is useful to review what the measurement means in a physiologic context, how the measurement is made, important limitations, and how this measurement may be helpful in common clinical scenarios. Compared with cardiac output measurement, Sv−O2 is more directly related to tissue oxygenation. Furthermore, when tissue oxygenation is a clinical concern, Sv−O2 is less prone to error compared with cardiac output, where small measurement errors may lead to larger errors in interpreting adequacy of oxygen delivery. ScvO2 should be measured from the tip of a central venous catheter placed close to, or within, the right atrium to reduce measurement error. Correct clinical interpretation of Sv−O2, or its properly measured ScvO2 surrogate, can be used to (1) estimate cardiac output using the Fick equation, (2) better understand whether a patient's oxygen delivery is adequate to meet their oxygen demands, (3) help guide clinical practice, particularly when resuscitating patients using validated early goal directed therapy treatment protocols, (4) understand and treat arterial hypoxemia, and (5) rapidly estimate shunt fraction (venous admixture).