No abstract was provided by the editors of this work

Bakker, Jan

Castro, Ricardo

Hagedorn, Jackie

Horowitz, James M.

Kaufman, David

Kozloff, Sam

Columbia University Academic Commons

Bakker et al. Crit Care          (2021) 25:269  https://doi.org/10.1186/s13054-021-03699-yRESEARCH LETTERBlood volume and albumin transudation in critically ill COVID-19 patientsJan Bakker1,2,3,4* , James M. Horowitz5, Jackie Hagedorn1, Sam Kozloff1, David Kaufman1 and Ricardo Castro4 © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.To the Editor:The SARS-CoV-2 infection (COVID-19) in critically ill patients presents as a viral pneumonia and inflammation affecting the endothelium [1] with unclear consequences for fluid leakage to the extravascular space. Neverthe-less, the adapted Surviving Sepsis Guidelines advocate a conservative fluid strategy [2]. By using a radiolabeled albumin tracer, the total blood volume (TBV), red blood cell volume (RBCV), plasma volume (PV), and the albu-min transudation rate (ATR) can be measured [3]. In six mechanically ventilated patients (admitted March/April 2020), the TBV was measured [4] as advanced hemody-namic monitoring was not used, and the volume status was unclear. The volumes measured were corrected for the ideal body weight of a corresponding healthy indi-vidual, and deviations were calculated. The results of only the TBV, RBCV, and PV were communicated with the treatment team.We retrospectively analyzed these data together with the ATR. Albumin transudation rate is presented as a numeric value with 0.0025 (0.25%/min exiting the cir-culation) serving as the normal reference threshold. We report absolute variation (values at admission minus value at day of measurement for each case), and day-indexed values, calculated by dividing the absolute vari-ation by the number of days in the ICU. We performed univariate regression between albumin transudation and variables of interest. In the multivariate regression, we tested variables that showed statistical significance in the univariate analysis and other that did not reach the significance threshold but had clinical relevance. Data are expressed as mean ± 1 standard deviation unless otherwise indicated. A p value of equal or less than 0.05 was considered significant. None of the patients was diagnosed with a secondary infection the days before the measurement. Age of the patients was 66 ± 11  year with a mean weight of 86.3 ± 15.7  kg. Only one patient did not have any comorbidity on admission where the most frequent comorbidity was diabetes (four patients, two in combination with hypertension). Four patients died, all of whom developed complete renal failure. At the time of measurement, all patients had stable hemo-dynamics only one patient received vasopressor support (norepinephrine 0.42 mcg/kg/min). Results are shown in Table 1. Three of the four clinically hypervolemic patients (assessed by fluid balance and extend of peripheral edema), TBV showed a decreased value from ideal body weight. The median ATR was 0.46%/min (range 0.12–0.82). There was a strong linear relationship between the day of admission and ATR  (R2 = 0.99, P < 0.0001) and a curve linear relationship with the deviation of the TBV  (R2 = 0.63, p < 0.03) (Fig. 1).In an exploratory multivariate regression model, we found TBV deviation (p = 0.022) and net fluid balance since admission (p = 0.018) and CRP at day of measure-ment (p = 0.043) to explain 99% of the variation in ATR.Although endothelial damage is believed to be an important part of COVID-19 and related to the severity of illness [5] and aggregates of red and white blood cells in the microcirculation have been reported [6], exten-sive capillary leakage has not been reported before. As a nosocomial bacterial infection had not been confirmed in any of the patients, the severity of COVID-19 and the Open Access*Correspondence:  jan.bakker@nyulangone.org1 Division of Pulmonary, Critical Care, and Sleep Medicine, New York University School of Medicine, New York, NY, USAFull list of author information is available at the end of the articlePage 2 of 4Bakker et al. Crit Care          (2021) 25:269 Table 1 Characteristics of individual patients at day of blood volume measurementMean ± SD and median (IQR 25, 75)% = being treated with norepinephrine, # = being treated with diuretic, S = survivor, NS = non-survivorHyper: hypervolemia, Eu: euvolemia, Hypo: hypovolemia. Total blood volume deviation: absolute and relative deviation of the expected total blood volume of a healthy individualParameter at time of measurement Pat 1#SPat 2%#NSPat 3NSPat 4NSPat 5#NSPat 6SMean ± SDMedian IQRICU Admission March2020March2020April2020April2020April2020April2020Day of ICU admission at measurement 14 20 11 13 7 2Age|male/female 70|M 69|M 49|M 62|M 66|F 81|M 66 ± 1168 (59–73)Height (cm) 1.75 1.73 1.65 1.73 1.58 1.52 166 ± 0.09 | 1.69 (1.57–1.74)Weight (kg) 76.2 78.0 77.8 67.8 93.9 61.8 75.9 ± 10.9 | 77.0 (66.3–82.0)Ideal body weight (kg) 70.0 69.0 61.0 69.0 51 50.0 61.7 ± 9.2 | 65.0 (50.8–69.3)Heart rate (b/min) 95 104 97 69 112 72 92 ± 1796 (71–106)Systolic arterial pressure (mmHg) 137 72 97 94 146 96 107 ± 2897 (89–138)Diastolic arterial pressure (mmHg) 56 38 66 48 52 42 50 ± 1050 (41–59)Mean arterial pressure (mm Hg) 79 50 76 66 75 58 67 ± 1171 (56–77)Lactate (mmol/L) 1.5 1.6 1.3 2.5 1.8 1.4 1.7 ± 0.41.6 (1.4–2.0)C reactive protein at measurement (mg/L) 3 239 409 282 263 50 208 ± 153251 (38–313)Inspired oxygen fraction 0.4 0.8 0.7 1 0.8 0.4 0.68 ± 0.240.75 (0.4–0.9)Pulse oximetry (%) 97 95 96 95 91 96 95 ± 296 (94–97)Net fluid balance day before measurement (L) − 0.9 1.2 1.3 − 0.3 − 0.9 3.0 0.6 ± 1.50.45 (− 0.9 to 1.7)Fluids IN day before measurement (L) 3.6 2.1 2.6 1.7 3.1 3.2 2.7 ± 0.72.9 (2.0–3.3)Urine output day before measurement (L) 4.5 0.7 0.8 2.7 1.8 0.7 1.9 ± 1.51.3 (0.7–3.2)Fluids in since admission (L) 36.8 41 17.2 19.8 15.4 3.8 22.3 ± 14.018.5 (12.5–37.9)Net fluid balance since admission (L) 8.2 10 5.9 3.0 0.3 4.0 5.2 ± 3.55.0 (2.3–8.7)Clinical assessment of volume status Hyper Hyper Eu Hyper Hyper HypoTotal blood volume (mL) 4200 4290 5360 3990 4870 4552 4544 ± 5024421 (4223–4791)Red cell volume (mL) 1215 935 1391 841 1220 1370 1162 ± 2271218 (1005–1333)Plasma volume (mL) 2985 3355 3969 3149 3650 3182 3382 ± 3663269 (3157–3576)Total blood volume dev (%) − 16.6 − 17.3 − 15.2 − 18.9 + 3.3 + 17.2 − 7.9 ± 14.8− 15.9 (− 17.7 to 6.8)Red cell volume dev (%) − 41% − 56% − 26% − 58% − 28% − 13% − 34 (− 56 to − 23)Plasma volume dev (%) − 0% 9% 44% 8% 21% 38% 15% (6–39)Albumin transudation rate (%/min) 0.58 0.82 0.43 0.49 0.24 0.12 0.45 ± 0.250.46 (0.21–0.64)Page 3 of 4Bakker et al. Crit Care          (2021) 25:269  systemic inflammatory response could be a more likely explanation. This vascular leakage could result in tis-sue edema and ultimately organ dysfunction as seen in these patients. Although this may suggest a role for the use of specific fluids (such as colloids) in this disease, our current data do not allow such recommendation. Given the only one-time measurement results should be interpreted with caution. This study could be seen as a unique exploratory study in COVID-19 patients. We have therefore initiated a multicenter prospective study to improve our understanding of blood volume and vascular leakage in critically ill COVID-19 patients (NCT04517695).AcknowledgementsNot applicable.Authors’ contributionsJB contributed to acquisition of data, the writing of the manuscript, analysis of the data, and construction of the figure and table. JMH, JH, and DK con-tributed to the writing of the manuscript. SK contributed to acquisition of data and the writing of the manuscript. RC contributed to the writing of the manuscript, analysis of the data, and the construction of the figure and table. All authors read and approved the final manuscript.FundingThe study was not supported. The prospective study that has started is sup-ported by the Daxor Company that performs the analysis of the samples for participating centers.Availability of data and materialsSupporting data are available upon request to the corresponding author 3 months after publication.DeclarationsEthics approval and consent to participateAs the measurements of blood volume were done on clinical indication and the retrospective analysis of the data did not contain patient-specific informa-tion, the IRB decided that this study did not require additional informed consent. The communication with the IRB on this topic is included as a supplement.Consent for publicationNot applicable.Competing interestsJB has received consulting grants from Daxor Company. Other authors have no competing interest to declare.Author details1 Division of Pulmonary, Critical Care, and Sleep Medicine, New York University School of Medicine, New York, NY, USA. 2 Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Sur-geons, New York, NY, USA. 3 Department of Intensive Care Adults, Erasmus MC University Medical Center, Rotterdam, Netherlands. 4 Department of Intensive Care, Pontificia Universidad Católica de Chile, Santiago, Chile. 5 Division of Car-diology, New York University School of Medicine, New York, NY, USA. Received: 30 March 2021   Accepted: 21 July 2021References 1. Pons S, Fodil S, Azoulay E, Zafrani L. The vascular endothelium: the cor-nerstone of organ dysfunction in severe SARS-CoV-2infection. Crit Care. 2020;24(1):353. 2. Alhazzani W, Moller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440–69.Fig. 1 Relationship between the albumin transudation rate (ATR) and the deviation of the total blood volume from ideal (TBV deviation)Page 4 of 4Bakker et al. Crit Care          (2021) 25:269 • fast, convenient online submission •  thorough peer review by experienced researchers in your field•  rapid publication on acceptance•  support for research data, including large and complex data types•  gold Open Access which fosters wider collaboration and increased citations  maximum visibility for your research: over 100M website views per year •  At BMC, research is always in progress.Learn more biomedcentral.com/submissionsReady to submit your research ?  Choose BMC and benefit from:  3. 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Blood volume and albumin transudation in critically ill COVID-19 patients

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Blood volume and albumin transudation in critically ill COVID-19 patients

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