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1.
Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial.
Tanaka, A, Shimabukuro, M, Teragawa, H, Okada, Y, Takamura, T, Taguchi, I, Toyoda, S, Tomiyama, H, Ueda, S, Higashi, Y, et al
Cardiovascular diabetology. 2021;(1):105
Abstract
BACKGROUNDS/AIM: Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). METHODS The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. RESULTS In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by - 2.23% (95% CI - 5.72 to 1.25) at week 4, - 8.07% (- 12.76 to - 3.37) at week 12, and - 5.60% (- 9.87 to - 1.32) at week 24; eEV by - 70.3 mL (95% CI - 136.8 to - 3.8) at week 4, - 135.9 mL (- 209.6 to - 62.3) at week 12, and - 144.4 mL (- 226.3 to - 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. CONCLUSIONS Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502.
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2.
Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial.
Hjortrup, PB, Haase, N, Bundgaard, H, Thomsen, SL, Winding, R, Pettilä, V, Aaen, A, Lodahl, D, Berthelsen, RE, Christensen, H, et al
Intensive care medicine. 2016;(11):1695-1705
Abstract
PURPOSE We assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock. METHODS We randomised 151 adult patients with septic shock who had received initial fluid resuscitation in nine Scandinavian ICUs. In the fluid restriction group fluid boluses were permitted only if signs of severe hypoperfusion occurred, while in the standard care group fluid boluses were permitted as long as circulation continued to improve. RESULTS The co-primary outcome measures, resuscitation fluid volumes at day 5 and during ICU stay, were lower in the fluid restriction group than in the standard care group [mean differences -1.2 L (95 % confidence interval -2.0 to -0.4); p < 0.001 and -1.4 L (-2.4 to -0.4) respectively; p < 0.001]. Neither total fluid inputs and balances nor serious adverse reactions differed statistically significantly between the groups. Major protocol violations occurred in 27/75 patients in the fluid restriction group. Ischaemic events occurred in 3/75 in the fluid restriction group vs. 9/76 in the standard care group (odds ratio 0.32; 0.08-1.27; p = 0.11), worsening of acute kidney injury in 27/73 vs. 39/72 (0.46; 0.23-0.92; p = 0.03), and death by 90 days in 25/75 vs. 31/76 (0.71; 0.36-1.40; p = 0.32). CONCLUSIONS A protocol restricting resuscitation fluid successfully reduced volumes of resuscitation fluid compared with a standard care protocol in adult ICU patients with septic shock. The patient-centred outcomes all pointed towards benefit with fluid restriction, but our trial was not powered to show differences in these exploratory outcomes. TRIAL REGISTRATION NCT02079402.
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3.
Sodium balance, not fluid balance, is associated with respiratory dysfunction in mechanically ventilated patients: a prospective, multicentre study.
Bihari, S, Peake, SL, Prakash, S, Saxena, M, Campbell, V, Bersten, A
Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2015;(1):23-8
Abstract
BACKGROUND Large positive sodium balances, independent of fluid balance, may lead to expanded extracellular fluid volumes and adverse clinical outcomes in the critically ill, including impaired oxygenation. OBJECTIVES To estimate sodium and fluid balances in critically ill patients needing invasive mechanical ventilation (MV) for more than 48 hours and to evaluate the relationship between fluid balance, sodium balance and respiratory function (PaO2/FiO2 ratio and length of MV). DESIGN AND SETTING A prospective, observational study of 50 patients on MV in four tertiary intensive care units. MAIN OUTCOME MEASURES Daily sodium and fluid input and output, biochemistry, haemodynamic variables, oxygenation (PaO2/FiO2) and steroid and vasopressor administration were recorded for 3 days after study enrolment. Outcome data included the duration of invasive MV, ICU and hospital mortality and ICU and hospital lengths of stay. RESULTS Fifty patients (33 men [66%]) with a mean age of 62.8 years (standard deviation, 14.6 years) and a median admission Acute Physiology and Chronic Health Evaluation III score of 82 (interquartile range [IQR], 61-99) were studied. By Day 3 after enrolment, the median cumulative fluid balance was 2668 mL (IQR, 875-3507 mL) and the cumulative sodium balance was +717 mmol (IQR, +422 to +958 mmol). Intravenous steroids and the presence of shock led to a lower daily sodium excretion (P=0.004 and P=0.01, respectively). A positive sodium balance was associated with a reduction in the next day's PaO2/FiO2 ratio (ρ=-0.36, P=0.001) and an increased length of MV (linear regression analysis, P<0.01). The cumulative fluid balance was not associated with either parameter. CONCLUSIONS The cumulative positive sodium balance, not the cumulative positive fluid balance, is associated with respiratory dysfunction and an increased length of MV.
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The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial.
Schramko, A, Suojaranta-Ylinen, R, Niemi, T, Pesonen, E, Kuitunen, A, Raivio, P, Salmenperä, M
Perfusion. 2015;(3):224-32
Abstract
INTRODUCTION Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. MATERIALS AND METHODS In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. RESULTS The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). CONCLUSIONS After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.
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5.
48-Hour Fluid Balance Does Not Predict a Successful Spontaneous Breathing Trial.
Antonio, AC, Teixeira, C, Castro, PS, Savi, A, Oliveira, RP, Gazzana, MB, Knorst, M
Respiratory care. 2015;(8):1091-6
Abstract
BACKGROUND Both premature and delayed liberation from mechanical ventilation are associated with increased morbidity and mortality, and fluid balance could negatively influence extubation outcomes. We sought to determine the impact of fluid balance in the 48 h before a spontaneous breathing trial (SBT) on weaning outcomes in a mixed ICU population. METHODS This was a prospective observational study in 2 adult medical-surgical ICUs. All enrolled subjects met eligibility criteria for weaning from mechanical ventilation. SBT failure was defined as inability to tolerate a T-piece trial for 30-120 min. Data on demographics, physiology, fluid balance in the 48 h preceding SBT (fluid input minus output over the 48-h period), lung ultrasound findings, and outcomes were collected. RESULTS Of a total of 250 SBTs, SBT failure eventuated in 51 (20.4%). Twenty-nine subjects (11.6%) had COPD, and 40 subjects (16%) were intubated due to respiratory sepsis. One-hundred eighty-nine subjects (75.6%) were extubated on the first attempt. Compared with subjects with SBT success, SBT failure subjects were younger (median of 66 vs. 75 y, P = .001) and had a higher duration of mechanical ventilation (median of 7 vs. 4 d, P < .001) and a higher prevalence of COPD (19.6 vs. 9.5%, P = .04). There were no statistically significant differences in 48-h fluid balance before SBT between groups (SBT failure, 1,201.65 ± 2,801.68 mL; SBT success, 1,324.39 ± 2,915.95 mL). However, in the COPD subgroup, we found a significant association between positive fluid balance in the 48 h before SBT and SBT failure (odds ratio of 1.77 [1.24-2.53], P = .04). CONCLUSIONS Fluid balance should not delay SBT indication because it does not predict greater probability of SBT failure in the medical-surgical critically ill population. Notwithstanding, avoiding positive fluid balance in patients with COPD might improve weaning outcomes. (ClinicalTrials.gov registration NCT02022839.).
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6.
Clinical Assessment of Fluid Balance is Incomplete for Colorectal Surgical Patients.
Tolstrup, J, Brandstrup, B
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. 2015;(3):161-8
Abstract
BACKGROUND AND AIMS Fluid balance for the surgical patient has been proven very important for the postoperative outcome and development of complications. The aim of this study was to evaluate, for the first time in modern times, the accordance between nurse-based fluid charting (cumulated fluid balance) and body weight change for general surgical patients. MATERIAL AND METHODS This was a descriptive study with prospectively collected data from two clinical randomized multicenter trials. A total of 113 patients from American Society of Anesthesiology group I-III undergoing elective colorectal surgery were included. Cumulated fluid balance and body weight change were charted preoperatively and daily at the same time during a postoperative period of 6 days. Differences were calculated by subtracting cumulated fluid balance from body weight change (1 g = 1 mL), and agreement was assessed by making Bland-Altman plots as well as Pearson correlations. RESULTS From day 1 to 4, the mean difference between cumulated fluid balance and body weight change was below 0.4 kg/L. On day 5 and 6, the discrepancies increased with mean differences of, respectively, 1.2 kg/L (p < 0.002*) and 2 kg/L (p < 0.0001*). Bland-Altman plots showed increasingly poor agreement for all postoperative days with wide limits of agreement, ranging from more than 6 kg/L to almost 10 kg/L. Pearson correlations were moderate to strong at all times ranging from 0.437 (day 1) to 0.758 (day 4). CONCLUSIONS The accordance between cumulated fluid balance and body weight change for colorectal surgical patients is relatively good for the first four postoperative days, however, with large uncertainty, whereas on the fifth and sixth postoperative day, the discrepancy is statistically and clinically significant. The fluid chart cannot stand alone in interpretation of the patient's fluid balance; body weight and clinical judgment is indispensable.
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A novel balanced isotonic sodium solution vs normal saline during major surgery in children up to 36 months: a multicenter RCT.
Disma, N, Mameli, L, Pistorio, A, Davidson, A, Barabino, P, Locatelli, BG, Sonzogni, V, Montobbio, G
Paediatric anaesthesia. 2014;(9):980-6
Abstract
BACKGROUND The use of isotonic electrolytic solutions for the intraoperative fluid management in children is largely recognized, but the exact composition still needs to be defined. OBJECTIVES The primary objective of this randomized controlled open trial was to compare the changes in chloride plasma concentration using two intraoperative isotonic fluid regimens (Sterofundin vs. normal saline, both added with 1% of glucose) in children undergoing major surgery. Secondary objectives were to compare changes in other electrolytes, renal function, and the occurrence of hypoglycemia. METHODS Children aged between 1 and 36 months, scheduled for major surgery, were randomized to receive Sterofundin or saline during the intraoperative time. Children with preoperative electrolyte abnormalities, hemodynamic instability, and severe renal or hepatic dysfunction were excluded. The primary outcome was the Δ of Cl(-) (Δ = change in plasma concentration between post- and pre-infusion), and secondary outcomes included Δ of other electrolytes and intraoperative hypoglycemia. RESULTS A total of 240 patients were included in the two study sites and randomized to receive Sterofundin plus 1% glucose or normal saline plus 1% glucose, in a open fashion (229 were finally analyzed). Δ of Cl- and Mg++ was statistically less relevant in patients who received intraoperative Sterofundin, and Δ of the other electrolytes was comparable between the two study groups. Relative risk of hyperchloremia was significantly higher when large volumes were infused (over than 46.7 ml·kg(-1) ), regardless of type of crystalloid infused. Hypoglycemia occurred in two of 229 patients. CONCLUSIONS Sterofundin is safer than normal saline in protecting young children undergoing major surgery against the risk of increasing plasma chlorides and the subsequent metabolic acidosis.
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8.
Fluid balance and urine volume are independent predictors of mortality in acute kidney injury.
Teixeira, C, Garzotto, F, Piccinni, P, Brienza, N, Iannuzzi, M, Gramaticopolo, S, Forfori, F, Pelaia, P, Rocco, M, Ronco, C, et al
Critical care (London, England). 2013;(1):R14
Abstract
INTRODUCTION In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI. METHODS We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression. RESULTS Of the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95%CI 0.12 to 0.52; <0.001). CONCLUSIONS In this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients.
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An observational study fluid balance and patient outcomes in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy trial.
, , Bellomo, R, Cass, A, Cole, L, Finfer, S, Gallagher, M, Lee, J, Lo, S, McArthur, C, McGuiness, S, et al
Critical care medicine. 2012;(6):1753-60
Abstract
OBJECTIVE To examine associations between mean daily fluid balance during intensive care unit study enrollment and clinical outcomes in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement therapy study. DESIGN Statistical analysis of data from multicenter, randomized, controlled trials. SETTING Thirty-five intensive care units in Australia and New Zealand. PATIENTS Cohort of 1453 patients enrolled in the RENAL study. INTERVENTIONS We analyzed the association between daily fluid balance on clinical outcomes using multivariable logistic regression, Cox proportional hazards, time-dependent analysis, and repeated measure analysis models. MEASUREMENTS AND MAIN RESULTS During intensive care unit stay, mean daily fluid balance among survivors was -234 mL/day compared with +560 mL/day among nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was -1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study treatment was independently associated with a decreased risk of death at 90 days (odds ratio 0.318; 95% confidence interval 0.24-0.43; p < .000.1) and with increased survival time (p < .0001). In addition, a negative mean daily fluid balance was associated with significantly increased renal replacement-free days (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p = .01). These findings were unaltered after the application of different statistical models. CONCLUSIONS In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes. Fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.
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10.
Vascular pedicle width in acute lung injury: correlation with intravascular pressures and ability to discriminate fluid status.
Rice, TW, Ware, LB, Haponik, EF, Chiles, C, Wheeler, AP, Bernard, GR, Steingrub, JS, Hite, RD, Matthay, MA, Wright, P, et al
Critical care (London, England). 2011;(2):R86
Abstract
INTRODUCTION Conservative fluid management in patients with acute lung injury (ALI) increases time alive and free from mechanical ventilation. Vascular pedicle width (VPW) is a non-invasive measurement of intravascular volume status. The VPW was studied in ALI patients to determine the correlation between VPW and intravascular pressure measurements and whether VPW could predict fluid status. METHODS This retrospective cohort study involved 152 patients with ALI enrolled in the Fluid and Catheter Treatment Trial (FACTT) from five NHLBI ARDS (Acute Respiratory Distress Syndrome) Network sites. VPW and central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP) from the first four study days were correlated. The relationships between VPW, positive end-expiratory pressure (PEEP), cumulative fluid balance, and PAOP were also evaluated. Receiver operator characteristic (ROC) curves were used to determine the ability of VPW to detect PAOP < 8 mmHg and PAOP ≥ 18 mm Hg. RESULTS A total of 71 and 152 patients provided 118 and 276 paired VPW/PAOP and VPW/CVP measurements, respectively. VPW correlated with PAOP (r = 0.41; P < 0.001) and less well with CVP (r = 0.21; P = 0.001). In linear regression, VPW correlated with PAOP 1.5-fold better than cumulative fluid balance and 2.5-fold better than PEEP. VPW discriminated achievement of PAOP < 8 mm Hg (AUC = 0.73; P = 0.04) with VPW ≤67 mm demonstrating 71% sensitivity (95% CI 30 to 95%) and 68% specificity (95% CI 59 to 75%). For discriminating a hydrostatic component of the edema (that is, PAOP ≥ 18 mm Hg), VPW ≥ 72 mm demonstrated 61.4% sensitivity (95% CI 47 to 74%) and 61% specificity (49 to 71%) (area under the curve (AUC) 0.69; P = 0.001). CONCLUSIONS VPW correlates with PAOP better than CVP in patients with ALI. Due to its only moderate sensitivity and specificity, the ability of VPW to discriminate fluid status in patients with acute lung injury is limited and should only be considered when intravascular pressures are unavailable.