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Elaine M Kaptein,1 Alan Cantillep,1 John S Kaptein,1 Zayar Oo,1 Myint B Thu,1 Phyu Phyu Thwe,1 Matthew J Kaptein1,2 1Department of Medicine, Division of Nephrology, University of Southern California, Los Angeles, CA, USA; 2Department of Medicine, Division of Nephrology, Loma Linda University Medical Center, Loma Linda, CA, USACorrespondence: Elaine M Kaptein Tel +1 213 220-0373Email ekaptein@usc.eduBackground: Accurate assessment of relative intravascular volume is critical for appropriate volume management of patients with kidney disease. Respiratory variations of inferior vena cava (IVC) diameter have been used and may correlate with those of subclavian vein (SCV) by bedside ultrasound. The purpose of this study was to assess the relationship between SCV and IVC respiratory variations by bedside ultrasound in a large group of hospitalized patients with acute and/or chronic kidney disease.Methods: We compared 160 paired SCV and IVC bedside ultrasound studies from 102 semi-recumbent hospitalized adult patients with kidney disease. Patient encounters in which the SCV or IVC could not be clearly visualized were excluded. Collapsibility index=(Dmax–Dmin)/Dmax*100%; D=venous diameter.Results: Relationships between SCV collapsibility index and IVC collapsibility index were not different for longitudinal and transverse views of the SCV. Correlation of SCV collapsibility index with IVC collapsibility index was 0.75 for mechanical ventilation (n=65, P< 0.0001) and 0.67 for spontaneous breathing (n=95, P< 0.0001). IVC collapsibility index cut-offs < 20% for hypervolemia and > 50% for hypovolemia corresponded to SCV collapsibility index cut-offs of < 22% and > 39%, respectively, for both mechanical ventilation and spontaneous breathing encounters. Using these cut-offs for SCV collapsibilities, assessment as hypervolemia versus not-hypervolemia had maximal sensitivity and specificity for predicting respective IVC collapsibility cut-offs of 88% for mechanical ventilation and 74% for spontaneous breathing, and assessment as hypovolemia versus not-hypovolemia had maximal sensitivity and specificity of 91% and 70%, respectively. Concordance, defined as agreement between assessment using SCV CI and assessment using IVC CI, was 85% for mechanical ventilation and 72% for spontaneous breathing when differentiating hypervolemia versus not-hypervolemia and was 89% and 71% respectively when differentiating hypovolemia versus not-hypovolemia.Conclusion: Assessment using SCV collapsibility index in the semi-recumbent position has a reasonable concordance with assessment using IVC collapsibility index for both spontaneous breathing and mechanical ventilation, in a wide range of hospitalized patients with concurrent kidney disease, and may be a useful adjunct to assess relative intravascular volume in patients with kidney disease.Keywords: acute kidney injury, chronic kidney disease, end-stage kidney disease, hospitalized patients, inferior vena cava ultrasound, intravascular volume assessment, point-of-care ultrasound, subclavian vein ultrasound, venous collapsibility index

Matthew J Kaptein,1,2 John S Kaptein,2 Zayar Oo,2 Elaine M Kaptein2 1Division of Nephrology, Loma Linda University Medical Center, Loma Linda, CA, USA; 2Division of Nephrology, University of Southern California, Los Angeles, CA, USA Background: Ultrasound (US) assessment of intravascular volume may improve volume management of dialysis patients. We investigated the relationship of intravascular volume evaluated by inferior vena cava (IVC) US to net volume changes with intermittent hemodialysis (HD) in critically ill patients. Methods: A retrospective cohort of 113 intensive care unit patients in 244 encounters had clinical assessment of intravascular volume followed by US of respiratory/ventilatory variation of IVC diameter, and had HD within 24 h. IVC collapsibility index (IVC CI)=(IVCmax–IVCmin)/IVCmax*100%. Volume management was guided by clinical data plus IVC US findings. Intradialytic hypotension (IDH) was categorized by severity from none to inability to tolerate HD. Results: Linear regression correlating n-weighted proportions of encounters achieving net volume removal of ≥0.5 L, ≥1.0 L, ≥1.5 L, and ≥2.0 L strongly correlated across the range of IVC CI (R2=0.87–0.64). Sensitivity and specificity analysis showed IVC CI was a better predictor than IVCmax of achieving net ultrafiltration (UF) volumes. Mean central venous pressure, pulmonary artery occlusion pressure, and cardiac output were poor predictors by logistic regression and receiver operating curve analyses. IVC CI

Hepatorenal syndrome (HRS) is a diagnosis of exclusion defined as acute kidney injury (AKI) with cirrhosis and ascites, with serum creatinine unresponsive to standardized volume administration and diuretic withdrawal. Persistent intravascular hypovolemia or hypervolemia may contribute to AKI and be revealed by inferior vena cava ultrasound (IVC US), which may guide additional volume management. Twenty hospitalized adult patients meeting HRS-AKI criteria had IVC US to assess intravascular volume after receiving standardized albumin administration and diuretic withdrawal. Six had IVC collapsibility index (IVC-CI) ≥50% and IVCmax ≤0.7 cm suggesting intravascular hypovolemia, 9 had IVC-CI <20% and IVCmax >0.7 cm suggesting intravascular hypervolemia, and 5 had IVC-CI ≥20% to <50% and IVCmax >0.7 cm. Additional volume management was prescribed in the 15 patients with either hypovolemia or hypervolemia. After 4-5 days, serum creatinine levels decreased ≥ 20% without hemodialysis in 6 of 20 patients - 3 with hypovolemia received additional volume, and 2 with hypervolemia plus one with 'euvolemia' and dyspnea were volume restricted and received diuretics. In the other 14 patients, serum creatinine failed to persistently decrease ≥20% or hemodialysis was required indicating that AKI did not improve. In summary, fifteen of 20 patients (75%) were presumed to have intravascular hypovolemia or hypervolemia by IVC ultrasound. Six of the 20 patients (40%) improved AKI by 4-5 days of follow-up with additional IVC US-guided volume management, and thus had been misdiagnosed as HRS-AKI. IVC US may more accurately define HRS-AKI as being neither hypovolemic nor hypervolemic, and guide volume management, decreasing the frequency of HRS-AKI misdiagnosis.

Goals of volume management are to accurately assess intravascular and extravascular volume and predict response to volume administration, vasopressor support or volume removal. Data are reviewed that support the following: (i) Dynamic parameters reliably guide volume administration and may improve clinical outcomes compared with static parameters, but some are invasive or only validated with mechanical ventilation without spontaneous breathing. (ii) Ultrasound visualization of inferior vena cava (IVC) diameter variations with respiration reliably assesses intravascular volume and predicts volume responsiveness. (iii) Although physiology of IVC respiratory variations differs with mechanical ventilation and spontaneous breathing, the IVC collapsibility index (CI) and distensibility index are interconvertible. (iv) Prediction of volume responsiveness by IVC CI is comparable for mechanical ventilation and spontaneous breathing patients. (v) Respiratory variations of subclavian/proximal axillary and internal jugular veins by ultrasound are alternative sites, with comparable reliability. (vi) Data support clinical applicability of IVC CI to predict hypotension with anesthesia, guide ultrafiltration goals, predict dry weight, predict intra-dialytic hypotension and assess acute decompensated heart failure. (vii) IVC ultrasound may complement ultrasound of heart and lungs, and abdominal organs for venous congestion, for assessing and managing volume overload and deresuscitation, renal failure and shock. (viii) IVC ultrasound has limitations including inadequate visualization. Ultrasound data should always be interpreted in clinical context. Additional studies are required to further assess and validate the role of bedside ultrasonography in clinical care., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Accurate assessment of relative intravascular volume is critical to guide volume management of patients with acute or chronic kidney disorders, particularly those with complex comorbidities requiring hospitalization or intensive care. Inferior vena cava (IVC) diameter variability with respiration measured by ultrasound provides a dynamic noninvasive point-of-care estimate of relative intravascular volume. We present details of image acquisition, interpretation, and clinical scenarios to which IVC ultrasound can be applied. The variation in IVC diameter over the respiratory or ventilatory cycle is greater in patients who are volume responsive than those who are not volume responsive. When 2 recent prospective studies of spontaneously breathing patients (n = 214) are added to a prior meta-analysis of 181 patients, for a total of 7 studies of 395 spontaneously breathing patients, IVC collapsibility index (CI) had a pooled sensitivity of 71% and specificity of 81% for predicting volume responsiveness, which is similar to a pooled sensitivity of 75% and specificity of 82% for 9 studies of 284 mechanically ventilated patients. IVC maximum diameter <2.1 cm, that collapses >50% with or without a sniff is inconsistent with intravascular volume overload and suggests normal right atrial pressure (0-5 mmHg). Inferior vena cava collapsibility (IVC CI) < 20% with no sniff suggests increased right atrial pressure and is inconsistent with overt hypovolemia in spontaneously breathing or ventilated patients. These IVC CI cutoffs do not appear to vary greatly depending on whether patients are breathing spontaneously or are mechanically ventilated. Patients with lower IVC CI are more likely to tolerate ultrafiltration with hemodialysis or improve cardiac output with ultrafiltration. Our goal for IVC CI generally ranges from 20% to 50%, respecting potential biases to interpretation and overriding clinical considerations. IVC ultrasound may be limited by factors that affect IVC diameter or collapsibility, clinical interpretation, or optimal visualization, and must be interpreted in the context of the entire clinical situation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiac output may increase after volume administration with relative intravascular volume depletion, or after ultrafiltration (UF) with relative intravascular volume overload. Assessing relative intravascular volume using respiratory/ventilatory changes in inferior vena cava (IVC) diameters may guide volume management to optimize cardiac output in critically ill patients requiring hemodialysis (HD) and/or UF.We retrospectively studied 22 critically ill patients having relative intravascular volume assessed by IVC Collapsibility Index (IVC CI) = (IVCmax-IVCmin)/IVCmax*100%, within 24 h of cardiac output measurement, during 37 intermittent and 21 continuous HD encounters. Cardiac output increase >10% was considered significant. Net volume changes between cardiac outputs were estimated from "isonatremic volume equivalent" (0.9% saline) gains and losses.Cardiac output increased >10% in 15 of 42 encounters with IVC CI <20% after net volume removal, and in 1 of 16 encounters with IVC CI ≥20% after net volume administration ( p  = 0.0136). All intermittent and continuous HD encounters resulted in intradialytic hypotension. Net volume changes between cardiac output measurements were significantly less (median +1.0 mL/kg) with intractable hypotension or vasopressor initiation, and net volume removal was larger (median -22.9 mL/kg) with less severe intradialytic hypotension ( p  < 0.001). Cardiac output increased >10% more frequently with least severe intradialytic hypotension and decreased with most severe intradialytic hypotension ( p  = 0.047).In summary, cardiac output may increase with net volume removal by ultrafiltration in some critically ill patients with relative intravascular volume overload assessed by IVC collapsibility. Severe intradialytic hypotension may limit volume removal with ultrafiltration, rather than larger volume removal causing severe intradialytic hypotension.

We propose that renal consults are enhanced by incorporating a nephrology-focused ultrasound protocol including ultrasound evaluation of cardiac contractility, the presence or absence of pericardial effusion, inferior vena cava size and collapsibility to guide volume management, bladder volume to assess for obstruction or retention, and kidney size and structure to potentially gauge chronicity of renal disease or identify other structural abnormalities. The benefits of immediate and ongoing assessment of cardiac function and intravascular volume status (prerenal), possible urinary obstruction or retention (postrenal), and potential etiologies of acute kidney injury or chronic kidney disease far outweigh the limitations of bedside ultrasonography performed by nephrologists. The alternative is reliance on formal ultrasonography, which creates a disconnect between those who order, perform, and interpret studies, creates delays between when clinical questions are asked and answered, and may increase expense. Ultrasound-enhanced physical examination provides immediate information about our patients, which frequently alters our assessments and management plans., Competing Interests: The authors have no financial interest in the subject matter.

Background: Wide ranges of sodium concentrations for different body fluid losses have been noted with minimal substantiating data and variability among sources, leading to use of "cumulative fluid balance" regardless of composition in hospitalized patients., Aims: To define the sodium concentrations of fluid losses from the body., Method: We performed a systematic search and literature review in adult humans using PubMed database., Results: Inclusion criteria were met for 107 full-text articles. Mean sodium concentrations were significantly lower for acidic (mean ± SD: 44 ± 12 mEq/L) than for alkaline (55 ± 13 mEq/L) gastric fluid, higher for bile (185 ± 24 mEq/L) or pancreatic fluid (156 ± 3 mEq/L) than for all other body fluids, and similar for intact small bowel (119 ± 14 mEq/L) and ileostomy outputs (116 ± 25 mEq/L). Sodium concentrations were significantly greater for cholera-induced diarrhea (128 ± 18 mEq/L) and lower for osmotic-induced diarrhea (28 ± 16 mEq/L) than all other causes of diarrhea. For osmotic diarrheas, sorbitol-induced diarrhea sodium concentration was higher (63 ± 17 mEq/L) than for carbohydrate malabsorption (43 ± 20 mEq/L), lactulose (26 ± 19 mEq/L), Idolax (16 ± 13 mEq/L), or polyethylene glycol (13 ± 7 mEq/L). For secretory diarrheas, sodium concentration for idiopathic causes (53 ± 22 mEq/L) was lower than for neuroendocrine and villous tumors (75 ± 13 mEq/L) or nonosmotic laxatives (88 ± 33 mEq/L). For pleural, peritoneal, and edema fluid, sodium concentrations (137 ± 13 mEq/L) were similar to plasma. No data were found for wound fluid. Sodium concentration for sweat was 44 ± 17 mEq/L., Conclusions: This is the first in-depth review of verifiable sodium concentrations of body fluids most commonly lost in hospitalized patients. Sodium concentrations are fluid-specific and consistent. Sodium concentrations for diarrhea are associated with specific mechanisms/causes. These data should be useful to more accurately replace sodium and water content for specific body fluid losses.
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Context: Elevated TSH with normal T4 frequently occurs with chronic kidney, liver, and heart diseases. Whether isolated TSH elevations represent mild thyroid gland failure has not been established., Evidence Acquisition: PubMed was searched for longitudinal studies in chronic heart, liver, or kidney disease documenting persistent isolated TSH elevations or progression to overt hypothyroidism., Evidence Synthesis: Four articles met inclusion criteria. In 16 end-stage renal failure patients, four had isolated TSH elevations. All normalized within 14 months. In 452 systolic heart failure patients, 20 had isolated TSH elevations, five of 20 were persistent, and none progressed to overt hypothyroidism within 6 months. In 207 untreated chronic hepatitis C patients, 12 had isolated TSH elevations and four had increased TSH with reduced free T4; all were female, and 14 had positive antithyroid antibodies. After 1 year, two of 12 developed "clinical hypothyroidism." In 72 chronic hepatitis C patients, nine females had positive antithyroid antibodies. Two antibody-negative patients had TSH 5-6 mU/L with reduced free T4. After 1 year, three of four with positive antithyroid antibodies and baseline TSH < 4 mU/L had elevated TSH with reduced free T4., Conclusions: In chronically ill patients, there is inadequate evidence to determine: 1) that isolated TSH elevations usually persist or progress to overt hypothyroidism; 2) the etiology and clinical significance of isolated TSH elevations; and 3) whether levothyroxine therapy is indicated for persistent isolated TSH elevations. Thus, isolated TSH elevations in chronic renal, cardiac, or liver diseases have not been documented to indicate mild thyroid gland failure.