Lung Ultrasound: A "Biomarker" for Fluid Overload?

Fluid overload is associated with poor outcomes in patients with acute kidney injury as well as end-stage kidney disease. Lung ultrasound (LUS) has been used in many different settings and specialties including the emergency department, intensive care unit, trauma, cardiology, and nephrology. Although LUS has been a valuable tool in assessing pulmonary congestion, LUS findings may not always be pathognomonic for pulmonary congestion. Furthermore, the feasibility of doing an extensive LUS examination as has been done in research studies may be hard to implement within the clinical setting. This review will go over the use of LUS to evaluate for fluid overload, compare LUS with other markers of fluid overload, review limitations of LUS, and suggest potential future directions in the use of LUS in nephrology.

Implementation of a decision aid for recognition and correction of volume alterations (Recova®) in haemodialysis patients.

BACKGROUND: Fluid overload is associated with mortality in haemodialysis patients, and 30% of patients remain fluid-overloaded after dialysis. The aim of this study was to evaluate if implementation of Recova®, a decision aid combining clinical assessment with bioimpedance spectroscopy, facilitates individualization of target weight determination and thereby contributes to improved fluid status in maintenance haemodialysis patients. METHODS: The impact of the implementation was measured as the proportion of participants at an adequate target weight at the end of the study, assessed as change in symptoms, hydration status, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Nurses were instructed to use Recova every 2 weeks, and the process of the intervention was measured as frequencies of fluid status assessments, bioimpedance measurements, and target weight adjustments. RESULTS: Forty-nine patients at two haemodialysis units were enrolled. In participants with fluid overload (n = 10), both overhydration and fluid overload symptom score decreased. In fluid-depleted participants (n = 20), target weight adjustment frequency and the estimated target weight increased. The post-dialytic negative overhydration was reduced, but NT-proBNP increased. CONCLUSIONS: Implementation of Recova in haemodialysis care increased the monthly frequencies of bioimpedance measurements and target weight adjustments, and it contributed to symptom reduction. TRIAL REGISTRATION: The Uppsala County Council Registry of Clinical Trials: FoU 2019-0001-15.

Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease.

BACKGROUND: Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. OBJECTIVES: We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. METHODS: We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using 23Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. RESULTS: CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = -0.5 ± 1.0 L; p = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4-31.3] vs. HC = 18.4 mmol/L [16.6-21.3]; p = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p = 0.26). Tissue sodium in both compartments correlated to FO (muscle: r = 0.63, p < 0.01; SC: rs = 0.63, p < 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p < 0.05), tumor necrosis factor-alpha (p < 0.01), and interleukin (IL)-6 (p = 0.01) and lower levels of vascular endothelial growth factor-C (p = 0.04). FO in CKD was linked to higher IL-8 (r = 0.51, p < 0.05) and inversely associated to E-selectin (r = -0.52, p = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p = 0.02). CONCLUSION: Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.

Relationship Between Total Body Protein and Cross-Sectional Skeletal Muscle Area in Liver Cirrhosis Is Influenced by Overhydration.

Sarcopenia as defined by reduced skeletal muscle area (SMA) on cross-sectional abdominal imaging has been proposed as an objective measure of malnutrition, and it is associated with both wait-list mortality and posttransplant complications in patients with cirrhosis. SMA, however, has never been validated against the gold standard measurement of total body protein (TBP) by in vivo neutron activation analysis (IVNAA). Furthermore, overhydration is common in cirrhosis, and its effect on muscle area measurement remains unknown. We aimed to examine the relationship between SMA and TBP in patients with cirrhosis and to assess the impact of overhydration on this relationship. Patients with cirrhosis who had undergone IVNAA and cross-sectional imaging within 30 days were retrospectively identified. Patients with significant clinical events between measurements were excluded. Psoas muscle area (PMA) and SMA at the level of the third lumbar vertebrae were determined. Total body water was estimated from a multicompartment model and expressed as a fraction of fat-free mass (FFM), as determined by dual-energy X-ray absorptiometry, to provide an index of hydration status. In total, 107 patients underwent 109 cross-sectional imaging studies (87 computed tomography; 22 magnetic resonance imaging) within 30 days of IVNAA. Median time between measurements was 1 day (IQR, -1 to 3 days). Between 43% and 69% of the cohort was identified as sarcopenic, depending on muscle area cutoff values used. TBP was strongly correlated with SMA (r = 0.78; P < 0.001) and weakly correlated with PMA (r = 0.49; P < 0.001). Multiple linear regression showed SMA was significantly and positively associated with FFM hydration (P < 0.001) independently of TBP. In conclusion, SMA is more closely related to TBP than is PMA, and it should be preferred as a measure of sarcopenia. Overhydration significantly affects the measurement of cross-sectional muscle area.

Effects of Volume Overload and Current Techniques for the Assessment of Fluid Status in Patients with Renal Disease.

Volume overload is an important, may be the foremost, independent prognostic factor determining the outcome of hemodialysis patients. Therefore, it is crucial to measure fluid status of these patients and avoid volume overload. This review aims to evaluate volume overload, its effects on patients with renal diseases and current methodologies measuring volume status in the body. These techniques will be first classified as clinical evaluation and non-clinical and/or instrumental techniques, which includes biomarkers, ultrasonography, relative blood volume monitoring, bioimpedance, echocardiography, pulmonary artery catheterization, esophageal and/or suprasternal Doppler, and blood viscosity. Advantages and limitations of these different techniques will be reviewed extensively by comparing each other. At last, insights gained from this review can highlight the future prospects in this active area of research.

The passage of fluid into the peritoneal cavity during hysteroscopy in pre-menopausal and post-menopausal patients.

The present study aimed to determine the amount of fluid medium passing through the Fallopian tubes into the peritoneal cavity during a hysteroscopy. This was done to understand the pathophysiology of complications related to the hysteroscopy. Conducted in a general hospital setting, the study examined the fluid inflow-outflow during a hysteroscopy both in pre- and post-menopausal women. A hysteroscopy was performed vaginoscopically for both diagnostic and therapeutic procedures. The study involved 117 patients. 84 (71.8%) of them were pre-menopausal and 33 (28.2%) were classified as post-menopausal. The fluid volume difference in the peritoneal cavity prior to hysteroscopy was 26.0 ± 4.2 mL in the pre-menopausal and 7.7 ± 2.4 mL (p = .001) in the post-menopausal group. The pre-menopausal group's flow rate through the Fallopian tubes was 1.5 ± 0.2 mL/min. In the post-menopausal group, it was 0.4 ± 0.1 mL/min (p < .05). It was found that during the hysteroscopy in the pre-menopausal patients, more fluid flows through the Fallopian tubes and at a higher flow rate. Impact statement What is already known on this subject? The complications during a hysteroscopy (HSC) are usually fluid-related and can result in adverse events such as a fluid overload, the dissemination of malignant cells, or electrolyte misbalance. Currently, there is a poor understanding of how HSC fluid behaviour impacts on the pathophysiology of these adverse procedure effects. What do the results of this study add? There have been no quantitative studies of the behaviour of fluid inside the uterine cavity during HSC, which means a quantification of fluid inflow and absorption is required. Our study adds a quantitative understanding of fluid behaviour during HSC. It shows increased rates of fluid passage, as well as fluid speed, into the peritoneal cavity in pre-menopausal patients. What are the implications of these findings for clinical practice and/or further research? Due to the higher rates of fluid passage and speed in pre-menstrual patients, caution regarding the complications during hysteroscopy and further studies are needed on the impact of different fluid distribution.

Use of Lung Ultrasound for the Assessment of Volume Status in CKD.

Adequate assessment of fluid status is an imperative objective in the management of all types of patients in cardiology, intensive care, and especially nephrology. Fluid overload is one of the most common modifiable risk factors directly associated with hypertension, heart failure, left ventricular hypertrophy, and eventually, higher morbidity and mortality risk in these categories of patients. Different methods are commonly used to determine fluid status (eg, clinical assessment, natriuretic peptide concentrations, echocardiography, inferior vena cava measurements, or bioimpedance analysis). In recent years, lung ultrasonography (LUS), through the assessment of extravascular lung water, has received growing attention in clinical research. This article summarizes available studies that compare LUS with other methods for fluid status assessment in patients with kidney diseases. At the same time, it also presents the association of LUS with different outcomes (physical functioning, mortality, and cardiovascular events) in the same population. It appears that this simple bedside noninvasive technique has significant clinical potential in nephrology.

Fluid status evaluation by inferior vena cava diameter and bioimpedance spectroscopy in pediatric chronic hemodialysis.

BACKGROUND: Evaluation of patient's dry weight remains challenging in chronic hemodialysis (HD) especially in children. Inferior Vena Cava (IVC) measurement was reported useful to assess fluid overload both in adults and children. METHODS: We performed a monocentric prospective study to evaluate the relation between predialytic IVC diameter measurements and hydration status evaluated by physicians and bioimpedance spectroscopy (BIS) and between IVC measurements and persistent hypertension. RESULTS: Forty-eight HD sessions in 16 patients were analyzed. According to physicians, patients were overhydrated in 84.5% of dialysis sessions, 20.8% according to BIS, and 0%, 4.1% and 20.8% according to IVC inspiratory, expiratory and collapsibility index reference curves respectively. There was no correlation between relative overhydration evaluated by BIS and IVC measurements z-scores (p = 0.20). Patients whose blood pressure normalized after HD had a more dilated maximal IVC diameter before dialysis session than patients with persistent hypertension (median - 0.07SD [-0.8; 0.88] versus -1.61SD [-2.18; -0.74] (p = 0.03)) with an optimal cut-off of -0.5 SD. CONCLUSIONS: In our study, IVC measurement is not reliable to assess fluid overload in children on HD and was not correlated with extracellular fluid volume assessed by BIS measurements. However, IVC measurements might be of interest in differentiating volume-dependant hypertension from volume-independant hypertension.

Lung ultrasound: a novel technique for detecting fluid overload in children on dialysis.

Background: Optimizing the target weight of infants and children on dialysis remains an important clinical challenge. The use of ultrasound to detect fluid overload in adult patients on dialysis is receiving growing attention. We hypothesized that fluid overload can be quantified in infants and children receiving dialysis using lung ultrasound. Methods: In this prospective observational study, infants and children receiving dialysis for end-stage renal disease (ESRD) or acute kidney injury (AKI) in a regional paediatric nephrology centre were eligible. Lung ultrasound examinations were performed during in-centre dialysis, on home visits or in an outpatient clinic. Fluid overload was assessed by quantifying B-lines on ultrasound and compared with proportional (%) increase in patient weight from the target weight. Results: A total of 142 ultrasound assessments were performed in 23 children. In children with AKI, median B-line score reduced from 5 (range 0-22) at presentation to 1.5 (0-4) at recovery (P = 0.04) with concurrent improvement in fluid overload judged by weight from 7.2 (-1.9 to 15.2)% to 0%. A linear correlation between lung ultrasound B-line score and fluid overload judged by weight was observed in children with AKI (r = 0.83) and ESRD (r = 0.61). Inter-observer variability was acceptable. Conclusions: Lung ultrasound is a practical and sensitive method of quantifying subclinical fluid overload in infants and children on dialysis. Interventional studies to determine the benefits of using lung ultrasound to optimize the target weight for children with ESRD are merited.

Fetal septum primum excursion (SPE) and septum primum excursion index (SPEI) as sonomarkers of fetal anemia: using hemoglobin Bart's fetuses as a study model.

OBJECTIVES: The objectives the study are to evaluate the effectiveness of septum primum excursion (SPE) and SPEI (SPE index, a ratio of SPE to left atrial diameter) in predicting fetal hemoglobin (Hb) Bart's disease and to determine the correlation between Hb levels and SPE/SPEI METHODS: The database of Cardio-STIC volume datasets (VDSs) of fetuses at risk of Hb Bart's disease at 18 to 22 weeks was assessed. The VDSs were blindly analyzed offline for measurements of SPE and SPEI. RESULTS: Of 180 VDSs recruited, 44 were acquired from fetuses with Hb Bart's disease, while 136 were derived from unaffected fetuses. SPE and SPEI was inversely correlated with Hb levels (p < 0.0001). The SPE and SPEI were significantly higher in the affected group (4.1 + 1.1 mm vs 3.0 + 0.8 mm and 0.61 + 1.1 vs 0.49.1 + 0.1, respectively). SPE, at cut-off 1.3 multiple of median, gave a sensitivity and specificity of 75.0% and 72.7%, respectively, but less than a sensitivity (81.4%) and specificity (95.4%) of middle cerebral artery peak systolic velocity. CONCLUSIONS: In anemic fetuses, SPE and SPEI was inversely correlated with Hb level. Additionally, SPE, better than SPEI, may be used as an adjunctive sonographic sign to predict Hb Bart's disease but its accuracy of prediction is not good enough to be used independently or as a diagnostic test. © 2016 John Wiley & Sons, Ltd.

The role of inferior vena cava diameter in volume status monitoring; the best sonographic measurement method?

OBJECTIVES: This study aims to determine the site of and the best sonographic method for measurement of inferior vena cava (IVC) diameter in volume status monitoring. METHODS: This observational before-and-after study was performed at the intensive care unit of the emergency department. It included hypotensive adult patients with suspected sepsis who were recommended to receive at least 20 mg/kg fluid replacement by the emergency physician. The patients were fluid replaced at a rate of 1000 mL/h, and maximum and minimum IVC diameters were measured and the Caval index calculated sonographically via both B-mode and M-mode. Hence, IVC's volume response was assessed by a total of 6 parameters, 3 each in M-mode and B-mode. Freidman test was used to assess the change in IVC diameter with fluid replacement. Wilcoxon test with Bonferroni correction was used to determine which measurement method more sensitively measured IVC diameter change. RESULTS: Twenty-eight patients with a mean age of 71.3 were included in the final analysis.The IVC diameter change was significant with all 6 methods (P < .001). The IVC minimum diameter change measured on M-mode during inspiration (M-mode i) was the only measurement method that significantly showed diameter change with each 500-mL fluid replacements. The initial and the subsequent M-mode i values after each 500 mL of fluid were 5.65 ± 3.34; 8.05 ± 3.66; 10.16 ± 3.61, and 11.21 ± 2.94, respectively (P < .001, P < .002, and P < .003, respectively). CONCLUSION: Inferior vena cava diameter was changed by fluid administration. The M-mode i method that most sensitively measures that change may be the most successful method in volume status monitoring.

From cerebral salt wasting to diabetes insipidus with adipsia: case report of a child with craniopharyngioma.

UNLABELLED: Craniopharyngioma is associated with a wide and interesting variety of sodium states both by itself and following surgical resection. These are often challenging to diagnose, especially given their dynamic nature during the perioperative course. We present the case of a boy with craniopharyngioma who had hyponatremia due to cerebral salt wasting preoperatively, developed diabetes insipidus (DI) intraoperatively and proceeded to develop hypernatremia with adipsic DI. CONCLUSION: Cerebral salt wasting is a rare presenting feature of craniopharyngioma. Postoperative DI can be associated with thirst abnormalities including adipsia due to hypothalamic damage; careful monitoring and a high index of suspicion are required for its detection. Adipsic DI is a difficult condition to manage; hence a conservative surgical approach is suggested.

Transesophageal echocardiography in the management of burn patients.

A systematic review was conducted to assess the level of evidence for the use of transesophageal echocardiography (TEE) in the management of burn patients. We searched any article published before and including June 30, 2013. Our search yielded 118 total publications, 11 met the inclusion criteria of burn injury and TEE. Available studies published in any language were rated and included. At the present time, there are no available systematic reviews/meta-analyses published that met our search criteria. Only a small number of clinical trials, all with a limited number of patients were available. Therefore, a meta-analysis on outcome parameters was not performed. However, the major pathologic findings in burn patients were reduced left ventricular (LV) systolic and diastolic function, mitral valve vegetation, pulmonary hypertension, pericardial effusion, fluid overload, and right heart failure. The advantages of TEE include offering direct assessment of cardiac valve competency, myocardial contractility, and most importantly real time assessment of adequacy of hemodynamic resuscitation and preload in the acute phase of resuscitation, with minimal additional risk. TEE serves multiple diagnostic purposes and is being used to better understand the fluid status and cardiac physiology of the critically ill burn patient. Randomized controlled trials especially on fluid resuscitation and cardiac performance in acute burns are warranted to potentially further improve outcome.

Venous collapsibility index changes in children on dialysis.

AIM: Hypervolemia is an important factor for the development of cardiac failure in end-stage renal disease. The aims of this study are to evaluate whether collapsibility index (CI) is a useful method to assess the volume status in children on haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), and to test whether the small amounts of fluid removed after a single dialysis exchange will be reflected by a change in CI in peritoneal dialysis patients. METHODS: Sixteen CAPD, nine HD patients aged from 5 to 18 years and 27 age- and sex-matched healthy children were enrolled in the study. Inferior vena cava diameters were measured from subxiphoidal long axis position in 2 cm to its junction to right atrium and CI were calculated. RESULTS: The collapsibility index was significantly lower in HD patients before HD and in the CAPD group before dialysate exchange when compared with the controls. No significant difference was found between the CAPD and HD groups. We observed significant increase in CI after HD, CI values reached nearly to control levels after HD. Ultrafiltrate was 1.93 +/- 0.98 kg in HD, 0.23 +/- 0.09 kg in the CAPD group. Although the change in CI values before and after dialysate exchange was significant in the CAPD group, there was still a significant difference between the CI values of the control group and the CAPD patients after dialysate exchange. CONCLUSION: We suggest that serial measurements of CI in children will be a useful guide to assess the volume changes in an individual instead of a single measurement.

Central pontine and extrapontine myelinolysis owing to disequilibrium syndrome.

Neurologic disorders can be seen in patients with end-stage renal failure owing to complications of hemodialysis or peritoneal dialysis. The disequilibrium syndrome can be seen, usually soon after or toward the end of dialysis. We report a patient with central pontine and extrapontine myelinolysis owing to disequilibrium syndrome. The patient had depressed consciousness, agitation, tremor, stupor and hyperactive deep tendon reflexes toward the end of the second peritoneal dialysis. A brain computed tomographic (CT) scan showed hypodense lesions in pontine and extrapontine locations without radiocontrast medium enhancement After 2 days, the patient had only minimal memory deficits. A control brain CT scan 1 week later showed a decrease of the lesions in central pontine and extrapontine locations. Central pontine and extrapontine myelinolysis should be suspected and investigated in the acute neurologic disorders of dialysis patients.

Fluid status, blood pressure, and cardiovascular abnormalities in patients on peritoneal dialysis.

OBJECTIVE: Hypertension, reduced arterial distensibility, and left ventricular hypertrophy (LVH) are risk factors for mortality in hemodialysis patients. However, few studies have focused on the relation between fluid status, blood pressure (BP), and cardiovascular abnormalities in peritoneal dialysis (PD) patients. This study was designed, first, to assess, using tracer dilution techniques, fluid status in PD patients compared to a control population of stable renal transplant (RTx) patients; second, to study the relation between fluid status, BP, and arterial wall abnormalities; third, to assess the determinants of cardiac structure; and last, to compare office and ambulatory BP measurements with respect to cardiac abnormalities. DESIGN: Cross-sectional study. SETTING: Multicenter study. PATIENTS: 41 stable PD patients with a mean Kt/V urea of 2.4 +/- 0.7, and 77 stable RTx patients. INTERVENTION: Fluid status was assessed by tracer dilution techniques: extracellular volume (ECV) with bromide dilution; total body water (TBW) with deuterium oxide; and plasma volume (PV) with dextran 70. Echocardiography was performed to assess left ventricular mass (LVM), left ventricular end diastolic diameter (LVEDD), and relative wall thickness as indicators of LVH. Echography of the common carotid artery was performed to assess arterial distensibility. Both office and 24-hour ambulatory BP measurements were performed. RESULTS: Fluid status, as assessed by ECV corrected for body surface area (BSA) (ECV:BSA), was significantly different between PD and RTx patients (9.4 +/- 2.6 vs 8.6 +/- 1.2 L/m2, p < 0.05). In 36.6% of the PD patients, ECV:BSA was above the 90th percentile of the RTx patients. Fluid status corrected for BSA, assessed by TBW (TBW:BSA), ECV (ECV:BSA), or plasma volume (PV:BSA), was significantly related to diastolic BP (DBP) (r = 0.35, r = 0.37, r = 0.53; p < 0.05). Arterial distensibility of the common carotid artery was related to systolic BP (SBP) (r = -0.36, p < 0.05). ECV was significantly related to LVEDD (r = 0.41, p < 0.05) as a marker of eccentric LVH, whereas arterial distensibility was related to relative wall thickness (r = -0.53, p < 0.001) as a marker of concentric LVH. An abnormal day-night BP rhythm, which was not related to fluid status, was observed in 68.4% of patients. Ambulatory DBP and SBP but not office DBP and SBP were related to LVM (r = 0.43, r = 0.46; p < 0.01). CONCLUSIONS: A large proportion of PD patients whose treatment prescriptions are in accordance with the Dialysis Outcomes Quality Initiative guidelines were found to be overhydrated compared with a population of stable RTx patients. Fluid status was significantly related to DBP and eccentric LVH, whereas arterial distensibility of the common carotid artery was significantly related to SBP and concentric LVH. In contrast to ambulatory BP, office BP was not related to LVM.

The postdialytic plasma cyclic guanosine 3':5'-monophosphate level as a measure of fluid overload in chronic hemodialysis.

The postdialytic plasma level of cGMP, a marker for the release of atrial natriuretic peptide (ANP) in humans, is closely related to hypervolemia in chronic hemodialysis patients. In order to test the practicability of routine postdialysis cGMP determination for the detection of fluid overload, ANP and cGMP levels in the total hemodialysis population of 81 patients were measured with blood samples drawn immediately after hemodialysis. Twenty-three patients had a cGMP level of more than 20 pmol/mL. In 13 of these, pulmonary congestion was present on the chest roentgenogram. Two of these patients refused a gradual reduction of their dry body weight. In the remaining 21 patients, the weight reduction was associated with a decrease in cGMP levels in all cases and with a decrease in ANP levels in all but two cases. Fourteen of the 21 patients reached a cGMP level below 20 pmol/mL after weight reduction, and at that time, none of these showed signs of pulmonary congestion on chest x-ray. All seven patients, whose cGMP levels remained above 20 pmol/mL despite the reduction, had documented heart disease with impairment of left ventricular function. These results suggest that the plasma cGMP level after hemodialysis is more apt for the determination of dry body weight than is ANP or a chest roentgenogram.