Comparison of Bioelectrical Impedance Analysis (BIA)-Derived Parameters in Healthy Volunteers and Critically Ill Patients.

OBJECTIVE: To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. DESIGN: Retrospective, observational data analysis. SETTING: Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). PATIENTS: 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. MEASUREMENTS AND MAIN RESULTS: Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). CONCLUSIONS: Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index.

Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome: A Narrative Review.

BACKGROUND: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. OBJECTIVES: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). METHODS: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. RESULTS: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. CONCLUSIONS: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice.

BACKGROUND: Sepsis is associated with generalised endothelial injury and capillary leak and has traditionally been treated with large volume fluid resuscitation. Some patients with sepsis will accumulate bodily fluids. The aim of this study was to systematically review the association between a positive fluid balance/fluid overload and outcomes in critically ill adults, and to determine whether interventions aimed at reducing fluid balance may be linked with improved outcomes. METHODS: We searched MEDLINE, PubMed, EMBASE, Web of Science, The Cochrane Database, clinical trials registries, and bibliographies of included articles. Two authors independently reviewed citations and selected studies examining the association between fluid balance and outcomes or where the intervention was any strategy or protocol that attempted to obtain a negative or neutral cumulative fluid balance after the third day of intensive care compared to usual care. The primary outcomes of interest were the incidence of IAH and mortality. RESULTS: Among all identified citations, one individual patient meta-analysis, 11 randomised controlled clinical trials, seven interventional studies, 24 observational studies, and four case series met the inclusion criteria. Altogether, 19,902 critically ill patients were studied. The cumulative fluid balance after one week of ICU stay was 4.4 L more positive in non-survivors compared to survivors. A restrictive fluid management strategy resulted in a less positive cumulative fluid balance of 5.6 L compared to controls after one week of ICU stay. A restrictive fluid management was associated with a lower mortality compared to patients treated with a more liberal fluid management strategy (24.7% vs 33.2%; OR, 0.42; 95% CI 0.32-0.55; P < 0.0001). Patients with intra-abdominal hypertension (IAH) had a more positive cumulative fluid balance of 3.4 L after one week of ICU stay. Interventions to decrease fluid balance resulted in a decrease in intra-abdominal pressure (IAP): an average total body fluid removal of 4.9 L resulted in a drop in IAP from 19.3 ± 9.1 mm Hg to 11.5 ± 3.9 mm Hg. CONCLUSIONS: A positive cumulative fluid balance is associated with IAH and worse outcomes. Interventions to limit the development of a positive cumulative fluid balance are associated with improved outcomes. In patients not transgressing spontaneously from the Ebb to Flow phases of shock, late conservative fluid management and late goal directed fluid removal (de-resuscitation) should be considered.

Association between different indexations of extravascular lung water (EVLW) and PaO2/FiO2: a two-center study in 231 patients.

BACKGROUND: Variability of body weight (BW) and height calls for indexation of volumetric hemodynamic parameters. Extravascular lung water (EVLW) has formerly been indexed to actual BW (BW(act)) termed EVLW-index (EVLWI). In overweight patients indexation to BW(act) might inappropriately lower indexed EVLWI(act). Several studies suggest indexation of EVLWI to predicted BW (EVLWI(pred)). However, data regarding association of EVLWI(act) and EVLW(pred) to mortality and PaO2/FiO2 are inconsistent. Two recent studies based on biometric database-analyses suggest indexation of EVLWI to height (EVLWI(height)). Therefore, our study compared the association of un-indexed EVLW, EVLWI(height), EVLW(pred) and EVLWI(act) to PaO2/FiO2 and Oxygenation index (OI = mean airway pressure*FiO2*/PaO2). METHODS: A total of 2119 triplicate transpulmonary thermodilutions (TPTDs; PiCCO; Pulsion Medical-Systems, Germany) were performed in 50 patients from the evaluation, and 181 patients from the validation groups. Correlations of EVLW and EVLWI to PaO2/FiO2, OI and ROC-AUC-analyses regarding PaO2/FiO2<200 mmHg (primary endpoint) and OI>10 were performed. RESULTS: In the evaluation group, un-indexed EVLW (AUC 0.758; 95%-CI: 0.637-0.880) and EVLWI(height) (AUC 0.746; 95%-CI: 0.622-0.869) provided the largest ROC-AUCs regarding PaO2/FiO2<200 mmHg. The AUC for EVLWI(pred) was smaller (0.713). EVLWI(act) provided the smallest AUC (0.685). This was confirmed in the validation group: EVLWI(height) provided the largest AUC (0.735), EVLWI(act) (0.710) the smallest. In the merged data-pool, AUC was significantly greater for EVLWI(height) (0.729; 95%-CI: 0.674-0.784) compared to all other indexations including EVLWI(act) (ROC-AUC 0.683, p = 0.007) and EVLWI(pred) (ROC-AUC 0.707, p = 0.015). The association of EVLW(I) was even stronger to OI compared to PaO2/FiO2. In the merged data-pool, EVLWI(height) provided the largest AUC regarding "OI>10" (0.778; 95%-CI: 0.713-0.842) compared to 0.739 (95%-CI: 0.669-0.810) for EVLWI(act) and 0.756 (95%-CI: 0.688-0.824) for EVLWI(pred). CONCLUSIONS: Indexation of EVLW to height (EVLWI(height)) improves the association of EVLW(I) to PaO2/FiO2 and OI compared to all other indexations including EVLWI(pred) and EVLWI(act). Also considering two recent biometric database analyses, EVLWI should be indexed to height.

Fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance.

INTRODUCTION: Capillary leak in critically ill patients leads to interstitial edema. Fluid overload is independently associated with poor prognosis. Bedside measurement of intra-abdominal pressure (IAP), extravascular lung water index (EVLWI), fluid balance, and capillary leak index (CLI) may provide a valuable prognostic tool in mechanically ventilated patients. METHODS: We performed an observational study of 123 mechanically ventilated patients with extended hemodynamic monitoring, analyzing process-of-care variables for the first week of ICU admission. The primary outcome parameter was 28-day mortality. ΔmaxEVLWI indicated the maximum difference between EVLWI measurements during ICU stay. Patients with a ΔmaxEVLWI <-2 mL/kg were called 'responders'. CLI was defined as C-reactive protein (milligrams per deciliter) over albumin (grams per liter) ratio and conservative late fluid management (CLFM) as even-to-negative fluid balance on at least two consecutive days. RESULTS: CLI had a biphasic course. ΔmaxEVLWI was lower if CLFM was achieved and in survivors (-2.4 ± 4.8 vs 1.0 ± 5.5 mL/kg, p = 0.001; -3.3 ± 3.8 vs 2.5 ± 5.3 mL/kg, p = 0.001, respectively). No CLFM achievement was associated with increased CLI and IAPmean on day 3 and higher risk to be nonresponder (odds ratio (OR) 2.76, p = 0.046; OR 1.28, p = 0.011; OR 5.52, p = 0.001, respectively). Responders had more ventilator-free days during the first week (2.5 ± 2.3 vs 1.5 ± 2.3, p = 0.023). Not achieving CLFM and being nonresponder were strong independent predictors of mortality (OR 9.34, p = 0.001 and OR 7.14, p = 0.001, respectively). CONCLUSION: There seems to be an important correlation between CLI, EVLWI kinetics, IAP, and fluid balance in mechanically ventilated patients, associated with organ dysfunction and poor prognosis. In this context, we introduce the global increased permeability syndrome.

Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment.

INTRODUCTION: Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI). METHODS: In this retrospective matched case-control study, we included 114 mechanically ventilated (MV) patients with ALI. We compared outcomes between a group of 57 patients receiving PAL-treatment (PAL group) and a matched control group, abstracted from a historical cohort. PAL-treatment combines high levels of positive end-expiratory pressure, small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix®) or ultrafiltration. Effects on extravascular lung water index (EVLWI), intra-abdominal pressure (IAP), organ function, and vasopressor therapy were recorded during 1 week. The primary outcome parameter was 28-day mortality. RESULTS: At baseline, no significant intergroup differences were found, except for lower PaO2/FIO2 and increased IAP in the PAL group (174.5 ± 84.5 vs 256.5 ± 152.7, p = 0.001; 10.0 ± 4.2 vs 8.0 ± 3.7 mmHg, p = 0.013, respectively). After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and cumulative fluid balance (-4.2 ± 5.6 vs -1.1 ± 3.7 mL/kg, p = 0.006; -0.4 ± 3.6 vs 1.8 ± 3.8 mmHg, p = 0.007; -1,451 ± 7,761 vs 8,027 ± 5,254 mL, p < 0.001). Repercussions on cardiovascular and renal function were limited. PAL-treated patients required fewer days of intensive care unit admission and days on MV (23.6 ± 15 vs 37.1 ± 19.9 days, p = 0.006; 14.6 ± 10.7 vs 25.5 ± 20.2 days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%, p = 0.034). CONCLUSION: PAL-treatment in patients with ALI is associated with a negative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes without compromising organ function.

Assessment of three minimally invasive continuous cardiac output measurement methods in critically ill patients and a review of the literature.

BACKGROUND: In this study we compared the accuracy of three continuous cardiac output (CCO) measurement methods, with intermittent transcardiopulmonary thermodilution (TPTD-CO) as the gold standard. The three studied CCO measurement methods were: uncalibrated peripheral pulse contour measurement (FCCO), calibrated central pulse contour measurement (PCCO), and CCO obtained by indirect Fick principle (NCCO). METHODS: We performed an observational study in 23 critically ill patients. Statistical analysis was done using Pearson's correlation and Bland-Altman analysis. A review of the relevant medical literature was performed. RESULTS: Only PCCO showed good correlation (R = 0.9) and agreement with a bias of 0.0 ± 0.8 L min⁻¹ and percentage error of 24.5% when compared to TPTD-CO. In patients with normal systemic vascular resistance index (SVRI > 1,700 dyne sec cm⁻5 m⁻²), NCCO (R = 0.8 and bias 0.4 ± 1.3 L min⁻¹) and FCCO (R = 0.8 and bias 0.1 ± 1 L min⁻¹) also produced reliable results. CONCLUSIONS: These results indicate that in our patient population, CCO can be most reliably monitored by calibrated central pulse contour measurements. All other methods appeared less accurate, especially in situations of low SVRI.

Exhaled carbon monoxide as a noninvasive marker of airway neutrophilia after lung transplantation.

BACKGROUND: Neutrophilic airway inflammation and associated oxidative stress contribute to airway injury and the development of bronchiolitis obliterans syndrome after lung transplantation (LTx). Exhaled carbon monoxide (eCO) reflects heme oxygenase-1 activity in response to oxidative stress. We investigated whether airway neutrophilia and eCO levels are associated in stable LTx recipients. METHODS: In this cross-sectional pilot study, 45 stable LTx recipients were included. During routine follow-up at the outpatient clinic, pulmonary function testings together with eCO measurements before broncho-alveolar lavage (BAL) were performed. BAL cell differentials and interleukin (IL)-8 protein levels were assessed and correlated with eCO. RESULTS: In the studied cohort, eCO levels were increased in patients with elevated (>3%) BAL neutrophilia compared with those with normal BAL neutrophilia (P=0.025). Furthermore, eCO levels significantly correlated with BAL neutrophilia and IL-8 levels in the cohort as a whole (r=0.50; P=0.0005 for total cells, r=0.43; P=0.003 for %cells and r=0.30; P=0.045 for IL-8). This was even more obvious in the LTx recipients with increased (>3%) BAL neutrophilia (r=0.70; P=0.0007 for total cells and r=0.80; P<0.0001 for %cells). For a cutoff of 4 ppm, sensitivity, specificity, positive and negative predictive value of eCO for detecting elevated BAL neutrophilia were 84.0%, 45.0%, 65.6%, and 69.2%, respectively (P=0.049). CONCLUSIONS: Elevated eCO levels in stable LTx recipients may reflect an increased BAL neutrophilia and could, therefore, be used as a noninvasive marker for airway inflammation after LTx.