key: cord-0709393-p1faflzb authors: Bakker, Jan; Horowitz, James M.; Hagedorn, Jackie; Kozloff, Sam; Kaufman, David; Castro, Ricardo title: Blood volume and albumin transudation in critically ill COVID-19 patients date: 2021-07-31 journal: Crit Care DOI: 10.1186/s13054-021-03699-y sha: 2c5e8f281517d78c7d6c855c2b194f9c2ac050e8 doc_id: 709393 cord_uid: p1faflzb nan 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. Nevertheless, 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 albumin transudation rate (ATR) can be measured [3] . In six mechanically ventilated patients (admitted March/April 2020), the TBV was measured [4] as advanced hemodynamic monitoring was not used, and the volume status was unclear. The volumes measured were corrected for the ideal body weight of a corresponding healthy individual, 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 circulation) serving as the normal reference threshold. We report absolute variation (values at admission minus value at day of measurement for each case), and dayindexed values, calculated by dividing the absolute variation 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 hemodynamics 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 (R 2 = 0.99, P < 0.0001) and a curve linear relationship with the deviation of the TBV (R 2 = 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 measurement (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] , extensive 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 systemic inflammatory response could be a more likely explanation. This vascular leakage could result in tissue 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). The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2infection Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19) TBV deviation) • 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 research ? Choose BMC Prediction of the normal blood volume. Relation of blood volume to body habitus Blood volume analysis: a new technique and new clinical interest reinvigorate a classic study Endothelial injury and glycocalyx degradation in critically ill coronavirus disease 2019 patients: implications for microvascular platelet aggregation Capillary leukocytes, microaggregates, and the response to hypoxemia in the microcirculation of coronavirus disease 2019 patients Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Not applicable. Authors' contributions JB 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 contributed 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. The study was not supported. The prospective study that has started is supported by the Daxor Company that performs the analysis of the samples for participating centers. Supporting data are available upon request to the corresponding author 3 months after publication. Ethics approval and consent to participate As the measurements of blood volume were done on clinical indication and the retrospective analysis of the data did not contain patient-specific information, 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. Not applicable. JB has received consulting grants from Daxor Company. Other authors have no competing interest to declare.