Liberal Fluid Research Articles

Abstract 4136967: Congestive Heart Failure Impedes Effective Fluid Resuscitation in Sepsis

Background: Fluid resuscitation is recommended in patients with sepsis. Sepsis, however, may be associated with myocardial dysfunction. Additionally, myocardial dysfunction and insufficient cardiac reserves in patients with congestive heart failure (CHF) may complicate fluid resuscitation in the setting of sepsis. We aimed to determine whether CHF would affect fluid resuscitation in septic patients admitted to intensive care unit. Outcome of patients with and without CHF were compared. Methods: Unmatched and propensity score matched septic patients with or without CHF were examined in a retrospective cohort of critically ill adults from the MIMIC-IV database by multivariable logistic regression. Mortality and length of stay were compared. Generalized additive models were used for assessing association between fluid resuscitation and in-hospital mortality. Results: Of 24,376 critically ill patients with sepsis, 6838 (28.1%) were also diagnosed with CHF. CHF in septic patients was associated with higher in-hospital mortality with an adjusted odds ratios of 1.25 (95% confidence interval (CI)=1.14-1.37; p<0.001) in unmatched analysis. Compared with patients without CHF, those with CHF had higher in-hospital mortality (14.3% vs. 9.8%, p < 0.001) and received less IV fluid in the first 24 hours of ICU stay (median=1936 ml, IQR=808-3654 vs. 3037, IQR=1810-4585 ml, p<0.001). Similar results were obtained in propensity score matched septic patients with or without CHF. We also found that fluid resuscitation had a U-shaped association with in-hospital mortality with a lowest mortality at roughly 60 ml/kg in the first 24 hours of ICU stay in septic patients without CHF. In septic patients with CHF, liberal fluid resuscitation did not reduce mortality, while restrictive fluid resuscitation was associated with an increased mortality rate. Conclusions: CHF was significantly associated with higher in-hospital mortality among septic patients. Adequate fluid resuscitation improved in-hospital mortality in septic patients without but not with CHF.

Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients (PRoFLUID)-study protocol for an international multicenter observational cohort study.

The practice of intravenous fluid and vasopressor therapy in intensive care unit (ICU) patients, particularly in those who receive invasive ventilation, has been subject to change. Traditional approaches of 'early and liberal fluid administration' and 'late and restrictive vasopressor use' have been challenged, leading to recommendations for giving less fluids and earlier administration of vasopressors. Recommendations for fluid deresuscitation-active fluid removal-are absent. The global approach to fluid and vasopressor therapy in invasively ventilated patients is currently unclear. Our aim is to explore the practice of intravenous fluid and vasopressor therapy in invasively ventilated ICU patients in a study named 'Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients' (PRoFLUID). PRoFLUID is an international, multicenter, observational cohort study in critically ill adult patients that are invasively ventilated for more than 24 hours. The outcomes include various aspects of fluid and vasopressor therapy, urine output and cumulative fluid balances. We will also collect duration of ventilation, lengths of stay and mortality in ICU and hospital. We expect to collect granular data on fluid and vasopressor therapy in a sample of at least 2,500 patients. PRoFLUID will provide useful insights into the practice of fluid and vasopressor therapy in invasively ventilated critically ill patients. PRoFLUID also allows us to determine whether geo-economic differences in management of intravenous fluid and vasopressor therapy exist, and allows for analyses of associations of aspects of fluid and vasopressor therapy with outcomes. Last but not least, its findings could feed sample size calculations of future randomized clinical trials of fluid and vasopressor therapy. In conclusion, PRoFLUID will collect data on fluid and vasopressor therapy in invasively ventilated ICU patients worldwide, providing insights that will guide future clinical decisions and randomized trial designs. ClinicalTrials.gov NCT05968066. Registered on August 1, 2023. Intensive care; invasive ventilation; fluid therapy; fluid management; vasopressor.

Major Publications in the Critical Care Pharmacotherapy Literature: 2023.

We aimed to summarize the most significant and impactful publications describing the pharmacotherapeutic care of critically ill patients in 2023. PubMed/MEDLINE and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. Randomized controlled trials and prospective studies of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2023, and December 31, 2023, were eligible for inclusion in this article. Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included. An a priori defined three-round modified Delphi process was employed to achieve consensus on the most impactful publications based on the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update returned a total of 1202 articles, of which 1164 were excluded. The remaining 38 articles underwent a three-round modified Delphi process. In each round, articles were independently scored based on overall contribution to scientific knowledge and novelty to the literature. Included articles are summarized and their impact discussed. Article topics included hydrocortisone for severe community-acquired pneumonia, inhaled amikacin for prevention of ventilator-associated pneumonia, methylene blue for septic shock, restrictive vs. liberal fluid management for sepsis-induced hypotension, andexanet alfa for major bleeding associated with factor Xa inhibitors, and early administration of four-factor prothrombin complex concentrate in patients with trauma at risk for massive transfusion. This review provides a summary and perspective on the potential impact of the most relevant articles in 2023 describing advances in the pharmacotherapeutic care of critically ill patients.

Joint Models Inform the Longitudinal Assessment of Patient-Reported Outcomes in Clinical Trials: A Simulation Study and Secondary Analysis of the Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery (RELIEF) Randomized Controlled Trial

Evaluate the utility of a joint model when analysing a patient-reported endpoint as part of a randomized controlled trial in which censoring occurs when patients die during follow-up. The present study comprises two parts: first we re-analyzed data from a previously published randomized controlled trial comparing two fluid regimens in the first 24 hours of major abdomino-pelvic surgery ('RELIEF' trial). In this trial, patient-reported disability was measured at multiple timepoints before and after surgery. Next, we conducted a simulation study to jointly emulate patient-reported disability and survival, similar to the RELIEF trial, under nine treatment-outcome scenarios. In both parts, we compared a joint model analysis to a linear mixed effect model combined with one of several traditional methods of handling longitudinal missingness: available data analysis, complete case analysis, last observation carried forward, and worst-case assumption. In part one, the joint model revealed no between-group differences in patient-reported disability at one, three, six, and 12 months after surgery. The worst-case approach consistently resulted in the largest deviation from the joint model estimates, although in this particular setting none of the approaches materially changed the study's conclusions. In part two, the simulations revealed that across all treatment-outcome scenarios, the joint model expectedly produced unbiased estimates of patient-reported disability. Similarly, employing an approach based on all available data (i.e., relying on the maximum likelihood estimator for handling missingness) yielded disability estimates close to the simulated values, albeit with slight bias across some scenarios. The last observation carried forward approach mirrored the joint model's estimates except when the treatment had a non-null effect on patient-reported disability. The worst case analysis resulted in high bias, which was particularly evident when the treatment had a large effect on survival. The complete case analysis resulted in high bias across all scenarios. In randomized trials that employ a patient-reported outcome as one of their endpoints, a joint model can address bias arising from informative missingness related to death. Methods for handling missingness based on all available data appear to be a reasonable alternative to joint models, with only slight bias across some simulated scenarios.

Liberal Fluid Resuscitation is Associated with Improved Outcomes in Pediatric Acute Pancreatitis

To evaluate outcomes of children from an observational cohort registry of index acute pancreatitis (AP) admissions managed with different types and rates of intravenous fluid therapy. Patients with index admission of AP between 2013 and 2023 were included. Those who received >1.5x the maintenance intravenous fluid rate were assigned to the liberal fluid group, and patients who received <1.5x maintenance fluids were assigned to the conservative group. Outcomes including intensive care unit admission rate, organ dysfunction, local pancreatic complications, and AP severity were evaluated. Influence of early enteral feeding and fluid composition on outcomes and clinical course were also analyzed. Patients who received liberal fluids were less likely to be admitted or transferred to the intensive care unit compared with those receiving conservative management (OR, 0.32; 95% CI, 0.12-0.80; P=.015). The liberal fluid group with early feeding had the lowest rate of moderate/severe manifestations of AP compared with other combinations of diet and fluid orders. Patients within the liberal fluid group who received the highest fluid rates (>2x maintenance) did not have higher rates of organ dysfunction or severe disease. Children with AP may stand to benefit from liberal fluid therapy and continued diet compared with more conservative fluid resuscitation and nothing by mouth status.

Effects of intraoperative different fluid therapy protocols on postoperative renal functions

PurposePlanning intraoperative fluid therapy in patients undergoing major abdominal surgery is important. It was aimed to define the difference between fluid therapy protocols for renal function, bleeding and postoperative service follow-ups.Materials and methodsThis is an observational case-controlled prospective study. Sixty patients aged 18–65 years who had undergone pancreatic surgery between December 2023– February 2023 were included in the study. Liberal (Group 1; n = 30) and targeted fluid therapies (Group 2; n = 30) were administered to the patients. Liberal fluid therapy was planned with 8–10 ml/kg/h crystalloid infusion. The targeted fluid therapy (TFT) group (Group 2; n = 30) began with a 2 ml/kg/h crystalloid infusion at the baseline. Additional fluid boluses were given in 250 ml of colloid infused over 10 min if PVI was > 13% for at least five minutes. The patients were staged using the KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The amount of bleeding during surgery was recorded for both groups.ResultsNo significant difference was observed in postoperative renal function. A significant difference was observed in the amount of intraoperative bleeding. The amount of bleeding was greater in patients managed with liberal fluid therapy. No significant difference was observed between the groups in the oral intake (hour), drain withdrawal (hour) mobilization (hour) and discharge (day) times and there isn’t any statistically significant differance between groups in cost effectivity (p>0.05).ConclusionKidney function was preserved during individualized targeted fluid therapy using non-invasive haemodynamic monitoring parameters.

The effect of high-volume intraoperative fluid administration on outcomes among pediatric patients undergoing living donor liver transplantation

BackgroundPediatric patients undergoing liver transplantation are particularly susceptible to complications arising from intraoperative fluid management strategies. Conventional liberal fluid administration has been challenged due to its association with increased perioperative morbidity. This study aimed to assess the impact of intraoperative high-volume fluid therapy on pediatric patients who are undergoing living donor liver transplantation (LDLT).MethodsConducted at the Children’s Hospital of Chongqing Medical University from March 2018 to April 2021, this retrospective study involved 90 pediatric patients divided into high-volume and non-high-volume fluid administration groups based on the 80th percentile of fluid administered. We collected the perioperative parameters and postoperative information of two groups. Multivariable logistic regression was utilized to assess the association between estimated blood loss (EBL) and high-volume FA. Kaplan-Meier survival analysis was used to compare patient survival after pediatric LDLT.ResultsPatients in the high-volume FA group received a higher EBL and longer length of stay than that in the non-high-volume FA group. Multivariate logistic regression analysis indicated that hours of maintenance fluids and fresh frozen plasma were significantly associated risk factors for the occurrence of EBL during pediatric LDLT. In addition, survival analysis showed no significant differences in one-year mortality between the groups.ConclusionsHigh-volume fluid administration during LDLT is linked with poorer intraoperative and postoperative outcomes among pediatric patients. These findings underscore the need for more conservative fluid management strategies in pediatric liver transplantations to enhance recovery and reduce complications.

Biomarker-guided acute kidney injury risk assessment under liberal versus restrictive fluid therapy - the prospective-randomized MAYDAY-trial

Acute kidney injury (AKI) prevalence in surgical patients is high, emphasizing the need for preventative measures. This study addresses the insufficient evidence on nephroprotective intraoperative fluid resuscitation and highlights the drawbacks of relying solely on serum creatinine/urine output to monitor kidney function. This study assessed the impact of intraoperative fluid management on AKI in female breast cancer patients undergoing autologous breast reconstruction, utilizing novel urinary biomarkers (TIMP-2 and IGFBP-7). In a monocentric prospective randomized controlled trial involving 40 patients, liberal (LFA) and restrictive (FRV) fluid management strategies were compared. TIMP-2 and IGFBP-7 biomarker levels were assessed using the NephroCheck (bioMerieux, France) test kit at preoperative, immediate postoperative, and 24-h postoperative stages. FRV showed significantly higher immediate postoperative biomarker levels, indicating renal tubular stress. FRV patients had 21% (4/19) experiencing AKI compared to 13% (2/15) in the LFA group according to KDIGO criteria (p = 0.385). Restrictive fluid resuscitation increases the risk of AKI in surgical patients significantly, emphasizing the necessity for individualized hemodynamic management. The findings underscore the importance of urinary biomarkers in early AKI detection.

Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial

BackgroundEarly fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD.MethodsThis post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90.ResultsOf 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29–0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0–7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9–8.1).ConclusionsIn patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy.Trial RegistrationNCT03434028 (2018-02-09), BioLINCC 14149.

Molecular Phenotyping of Patients with Sepsis and Kidney Injury and Differential Response to Fluid Resuscitation.

Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial. We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction. Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen's Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) (p-value-for-interaction = 0.03). Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.

The effect of restrictive compared to liberal intravenous fluid volume on hypotension in adults undergoing major abdominal surgery

In a cardiac output (CO) sub-study of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial, it was shown that restrictive fluid management was associated with lower cardiac index at the end of surgery. However, the association of the fluid protocol with intraoperative blood pressure was less clear. This paper primarily compares rates of hypotension between the two fluid regimens. The haemodynamic effects of these protocols may increase our understanding of perioperative fluid prescription. Using a data set of arterial pressure and cardiac output measurements, this observational cohort study primarily compares intraoperative hypotension rates defined by a mean arterial pressure < 65 mmHg between liberal and restrictive fluid protocols. Secondary analyses explore predictors of invasive mean arterial pressure and doppler-derived cardiac output, including fluid volume regimens and surgical duration. 105 patients had a combined total of 835 haemodynamic data capture events from the beginning to the end of the surgery. Here we report that a restrictive regimen is not associated with a greater proportion of participants who experience at least one episode of hypotension than the liberal regimen 64.1% vs. 61.5% (mean difference 2.6%, 95% CI − 15.9% to 21%, p = 0.78). Duration of surgery was associated with an increased risk of hypotension (OR 1.05, 1 to 1.1, p = 0.038). A fluid restriction protocol compared to liberal fluid administration is not associated with lower blood pressure.

The effect of liver surgery and fluid strategy on renin activity and aldosterone and anti-diuretic hormone levels: a secondary analysis of the GALILEO trial

BackgroundIt is unknown whether liver surgery leads to increased RAAS activity and anti-diuretic hormone (ADH) levels and subsequent fluid accumulation. Furthermore, it is unknown whether the peri-operative fluid strategy changes this effect. MethodsThis is a pre-planned post hoc analysis of a randomised controlled trial which compared restrictive (n = 20) versus liberal fluid strategy (n = 20) in patients undergoing liver surgery. Primary outcomes for the current study were the difference in hormone levels after anaesthesia induction and after liver resection. Fluid overload was defined as a ≥10% increase in weight. ResultsRenin activity (6 [2.1–15.5] vs. 12 [4.6–33.5]) and ADH levels (6.0 [1.7–16.3] vs. 3.8 [1.6–14.7]) did not differ significantly before and after resection. However, aldosterone levels were significantly higher after resection (0.30 [0.17–0.49] vs. 0.69 [0.31–1.21] ). Renin activity and aldosterone levels did not differ between the groups. ADH was significantly higher in the restrictive strategy group (1.6 [1.1–2.1] vs 5.9 [3.8–16.0]). No differences in hormone levels were found in patients with and without fluid overload. DiscussionAldosterone levels increased after liver surgery but renin activity and ADH levels did not. ADH levels were higher in the restrictive group. Development of post-operative fluid overload was not associated with RAAS activity or ADH levels.

Prothrombin and activated partial thromboplastin times, thromboelastography, hematocrit, and platelet count in a feline hemorrhage/over-resuscitation model using lactated Ringer's solution or 6% tetrastarch 130/0.4.

To describe and compare prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG), HCT, and platelet count measurements in a hemorrhage/over-resuscitation model. Randomized crossover study. University teaching hospital. Six cats. Anesthetized cats underwent 3 treatments at 2-month intervals. The treatments were as follows: NHR-no controlled hemorrhage and sham resuscitation; LRS-controlled hemorrhage and lactated Ringer's solution (LRS) for resuscitation; and Voluven-controlled hemorrhage and 6% tetrastarch 130/0.4 for resuscitation. The LRS and Voluven were administered at 60 and 20mL/kg/h, respectively, for 120minutes. Blood samples were drawn for PT, aPTT, TEG, HCT, and platelet count measurements at a healthy check (T - 7d), after controlled hemorrhage (T0), at 60 and 120minutes of resuscitation (T60 and T120), and at 24hours after completion of resuscitation (T24h). Data were analyzed using a general linear mixed model approach (significance was P<0.05). Total median blood loss (controlled hemorrhage and blood sampling from T0 to T120) at T120 was 11.4, 31.0, and 30.8mL/kg for NHR, LRS, and Voluven, respectively. PT and aPTT during LRS and Voluven were prolonged at T60 and T120 compared to NHR (P<0.001). On TEG, the reaction time, kinetic time, and alpha-angle were within reference intervals for cats at all time points in all treatments, while maximum amplitude was less than the reference interval (40mm) at T0, T60, and T120 during Voluven and at T60 and T120 during LRS compared to NHR (both P<0.001). The HCT and platelet count were significantly lower at T60 and T120 during LRS and Voluven compared to NHR (P<0.001). Hypocoagulopathy was observed during hemorrhage and liberal fluid resuscitation. Prolongation of PT and aPPT and decreased clot strength may have been caused by hemodilution and platelet loss.

Identifying novel clinical phenotypes of acute respiratory distress syndrome using trajectories of daily fluid balance: a secondary analysis of randomized controlled trials

BackgroundPreviously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification.MethodsFACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial.ResultsUsing JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p < 0.001), and fewer ventilator-free days (0 vs. 20, p < 0.001). A significant HTE between phenotypes and fluid management strategies was observed in the FACTT. An 8-variables model was derived for phenotype assignment.ConclusionsWe identified and validated two novel clinical trajectories for ARDS patients, with both prognostic and predictive enrichment. The trajectories of ARDS can be identified with simple classifier models.

A double-blinded randomised controlled study of fluid restriction versus liberal fluid during induction of labour: A pilot study.

Excess intravenous fluid for women requiring an induction of labour may adversely affect the duration of labour and maternal/neonatal outcomes. This study aimed to determine the difference in duration of labour and outcomes with a low background infusion rate, compared to liberal background intravenous fluid management. A double blind randomised controlled pilot study was performed on 200 women who underwent induction of labour at a single institution. Women were randomised to an intravenous rate of 40 mL/h versus 250 mL/h of Hartmann's solution. Fluid boluses were strictly controlled to limit bias. This trial was registered with the Australian clinical trial registry: ACTRN12621001298808. Analysis of the total amount of fluid received showed good separation with Group 1 (40 mL/h) receiving 1,736 mL less than Group 2 (250 mL/h), median (interquartile range) 841 mL (458, 1691) versus 2,577 mL (1620, 4326) (P < 0.001). Median duration of labour was shorter in Group 1 by 24 min (P = ns). Subset analysis of nulliparous women showed that duration of labour was shorter in Group 1 by 83.5 min (P = ns). As this was a pilot study, a significant difference in duration of labour or secondary outcomes was not seen. Given the increasing numbers of nulliparous women having an induction of labour, potential for adverse maternal and neonatal outcomes and the associated higher rate of operative birth, this study guides power calculations and supports proof of concept for future research into optimum fluid management during induction of labour for these women.

Impact of fluid balance and opioid-sparing anesthesia within enchanced recovery pathway on postoperative morbidity after transthoracic esophagectomy for cancer.

BackgroundEnhanced Recovery After Surgery (ERAS) protocol for esophagectomy may reduce the high incidence of postoperative morbidity and mortality. The aim of this study was to assess the impact of properly conducted ERAS protocol with specific emphasis on fluid balance and opioid-sparing anesthesia (OSA) on postoperative major morbidity and mortality after esophagectomy.MethodsPatients undergoing elective esophagectomy for esophageal cancer at the Hospital for Digestive Surgery, University Clinical Center of Serbia, from December 2017 to March 2021, were included in this retrospective observational study. Patients were divided into two groups: the ERAS group (OSA, intraoperative goal-directed therapy, and postoperative “near-zero” fluid balance) and the control group (opioid-based anesthesia, maintenance mean blood pressure ≥ 65 mmHg, and liberal postoperative fluid management). The primary outcome was major morbidity within 30 days from surgery and 30-day and 90-day mortality. Multivariable analysis was used to examine the effect of the ERAS protocol.ResultsA total of 121 patients were divided into the ERAS group (69 patients) and the control group (52 patients). Patients in the ERAS group was received less fentanyl, median 300 (interquartile range (IQR), 200–1,550) mcg than in control group, median 1,100 (IQR, 650–1750) mcg, p &amp;lt; 0.001. Median intraoperative total infusion was lower in the ERAS group, 2000 (IQR, 1000–3,750) mL compared to control group, 3,500 (IQR, 2000–5,500) mL, p &amp;lt; 0.001. However, intraoperative norepinephrine infusion was more administered in the ERAS group (52.2% vs. 7.7%, p &amp;lt; 0.001). On postoperative day 1, median cumulative fluid balance was 2,215 (IQR, −150-5880) mL in the ERAS group vs. 4692.5 (IQR, 1770–10,060) mL in the control group, p = 0.002. After the implementation of the ERAS protocol, major morbidity was less frequent in the ERAS group than in the control group (18.8% vs. 75%, p &amp;lt; 0.001). There was no statistical significant difference in 30-day and 90-day mortality (p = 0.07 and p = 0.119, respectively). The probability of postoperative major morbidity and interstitial pulmonary edema were higher in control group (OR 5.637; CI95%:1.178–10.98; p = 0.030 and OR 5.955; CI95% 1.702–9.084; p &amp;lt; 0.001, respectively).ConclusionA major morbidity and interstitial pulmonary edema after esophagectomy were decreased after the implementation of the ERAS protocol, without impact on overall mortality.

Management Changes After Echocardiography Are Associated With Improved Outcomes in Critically Ill Children.

To evaluate management changes and outcomes in critically ill children after formal echocardiography. Retrospective cohort study between January 1, 2011, and December 31, 2020. Tertiary care children's hospital. Patients from 1 to 18 years who had formal echocardiography within 72 hours of ICU admission and who were intubated and on vasoactive infusions at the time of the study. Patients were stratified into two cardiac function groups: 1) near-normal cardiac function and 2) depressed cardiac function. Clinical variables were abstracted from the electronic medical record and placed in time sequence relative to echocardiography. Vasoactive and fluid management strategies in place before echocardiography were associated with markers of tissue perfusion and volume overload. Management changes after echocardiography were characterized and associated with outcomes. None. Among patients eventually found to have depressed cardiac function, the use of vasoconstrictors was associated with worse lactate clearance and oxygen extraction ratio. Use of vasoconstrictors in this cohort was also associated with a more liberal fluid management strategy, evidence of increased lung water, and a worse Sp o2 /F io2 . An echocardiogram demonstrated depressed cardiac function was likely to be followed by management changes that favored inotropes and more conservative fluid administration. Patients with depressed cardiac function who were switched to inotropes were more likely to be extubated and to wean off vasoactive support compared with those patients who remained on vasoconstrictors. Among patients with depressed cardiac function, alterations in management strategy after echocardiography are associated with shortened duration of intensive care interventions.

Candidate Kidney Protective Strategies for Patients Undergoing Major Abdominal Surgery: A Secondary Analysis of the RELIEF Trial Cohort.

Acute kidney injury (AKI) is common after major abdominal surgery. Selection of candidate kidney protective strategies for testing in large trials should be based on robust preliminary evidence. A secondary analysis of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial was conducted in adult patients undergoing major abdominal surgery and randomly assigned to a restrictive or liberal perioperative fluid regimen. The primary outcome was maximum AKI stage before hospital discharge. Two multivariable ordinal regression models were developed to test the primary hypothesis that modifiable risk factors associated with increased maximum stage of postoperative AKI could be identified. Each model used a separate approach to variable selection to assess the sensitivity of the findings to modeling approach. For model 1, variable selection was informed by investigator opinion; for model 2, the Least Absolute Shrinkage and Selection Operator (LASSO) technique was used to develop a data-driven model from available variables. Of 2,444 patients analyzed, stage 1, 2, and 3 AKI occurred in 223 (9.1%), 59 (2.4%), and 36 (1.5%) patients, respectively. In multivariable modeling by model 1, administration of a nonsteroidal anti-inflammatory drug or cyclooxygenase-2 inhibitor, intraoperatively only (odds ratio, 1.77 [99% CI, 1.11 to 2.82]), and preoperative day-of-surgery administration of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker compared to no regular use (odds ratio, 1.84 [99% CI, 1.15 to 2.94]) were associated with increased odds for greater maximum stage AKI. These results were unchanged in model 2, with the additional finding of an inverse association between nadir hemoglobin concentration on postoperative day 1 and greater maximum stage AKI. Avoiding intraoperative nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors is a potential strategy to mitigate the risk for postoperative AKI. The findings strengthen the rationale for a clinical trial comprehensively testing the risk-benefit ratio of these drugs in the perioperative period.

Goal-directed fluid therapy guided by plethysmographic variability index versus conventional liberal fluid therapy in neonates undergoing abdominal surgery: A prospective randomized controlled trial.

Intraoperative fluid therapy maintains normovolemia, normal tissue perfusion, normal metabolic function, normal electrolytes, and acid-base status. Plethysmographic variability index has been shown to predict fluid responsiveness but its role in guiding intraoperative fluid therapy is still elusive. The aim of the present study was to compare intraoperative goal-directed fluid therapy based on plethysmographic variability index with liberal fluid therapy in term neonates undergoing abdominal surgeries. A prospective randomized controlled study was conducted in a tertiary care centre, over a period of 18 months. A total of 30 neonates completed the study out of 132 neonates screened. Neonates with tracheoesophageal fistula, congenital diaphragmatic hernia, congenital heart disease, respiratory disorders, creatinine clearance <90 mL/min and who were hemodynamically unstable were excluded. Neonates were randomized to goal-directed fluid therapy group where the plethysmographic variability index was targeted at <18 or liberal fluid therapy group. Primary outcome was comparison of total amount of fluid infused intraoperatively in both the groups. Secondary outcomes included intraoperative and postoperative arterial blood gas parameters, biochemical parameters, use of vasopressors, number of fluid boluses, complications and duration of hospital stay. There was no significant difference in total intraoperative fluid infused [90 (84-117.5 mL) in goal-directed fluid therapy and 105 (85.5-144.5 mL) in liberal fluid therapy group (p = .406)], median difference (95% CI) -15 (-49.1 to 19.1). There was a decrease in serum lactate levels in both groups from preoperative to postoperative 24 h. The amount of fluid infused before dopamine administration was significantly higher in liberal fluid therapy group (58 [50.25-65 mL]) compared to goal-directed fluid therapy group (36 [22-44 mL], p = .008), median difference (95% CI) -22 (-46 to 2). In postoperative period, the total amount of fluid intake over 24 h was comparable in two groups (222 [204-253 mL] in goal-directed fluid therapy group and 224 [179.5-289.5 mL] in liberal fluid therapy group, p = .917) median difference (95% CI) cutoff -2 (-65.3 to 61.2). Intraoperative plethysmographic variability index-guided goal-directed fluid therapy was comparable to liberal fluid therapy in terms of total volume of fluid infused in neonates during perioperative period. More randomized controlled trials with higher sample size are required. Central Trial Registry of India (CTRI/2020/02/023561).

Perioperative Fluid Management in Colorectal Surgery: Institutional Approach to Standardized Practice

The present review discusses restrictive perioperative fluid protocols within enhanced recovery after surgery (ERAS) pathways. Standardized definitions of a restrictive or liberal fluid regimen are lacking since they depend on conflicting evidence, institutional protocols, and personal preferences. Challenges related to restrictive fluid protocols are related to proper patient selection within standardized ERAS protocols. On the other hand, invasive goal-directed fluid therapy (GDFT) is reserved for more challenging disease presentations and polymorbid and frail patients. While the perfusion rate (mL/kg/h) appears less predictive for postoperative outcomes, the authors identified critical thresholds related to total intravenous fluids and weight gain. These thresholds are discussed within the available evidence. The authors aim to introduce their institutional approach to standardized practice.