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Fluids, fluids everywhere, but do we stop to think?

Kaufman, David A
PMID: 37573158
ISSN: 1557-8615
CID: 5619132

The Ins and Outs of IV Fluids in Hemodynamic Resuscitation

Kaufman, David A; Lopes, Marcela; Maviya, Niharika; Magder, Sheldon A
OBJECTIVES:Concise definitive review of the physiology of IV fluid (IVF) use in critically ill patients. DATA SOURCES:Available literature on PubMed and MEDLINE databases. STUDY SELECTION:Basic physiology studies, observational studies, clinical trials, and reviews addressing the physiology of IVF and their use in the critically ill were included. DATA EXTRACTION:None. DATA SYNTHESIS:We combine clinical and physiologic studies to form a framework for understanding rational and science-based use of fluids and electrolytes. CONCLUSIONS:IVF administration is among the most common interventions for critically ill patients. IVF can be classified as crystalloids or colloids, and most crystalloids are sodium salts. They are frequently used to improve hemodynamics during shock states. Many recent clinical trials have sought to understand which kind of IVF might lead to better patient outcomes, especially in sepsis. Rational use of IVF rests on understanding the physiology of the shock state and what to expect IVF will act in those settings. Many questions remain unanswered, and future research should include a physiologic understanding of IVF in study design.
PMID: 37707377
ISSN: 1530-0293
CID: 5593232

INFLUENCE OF INFLAMMATORY MARKERS AND ACUTE PHASE REACTANTS ON PULMONARY DEAD SPACE IN COVID-19 ARDS [Meeting Abstract]

Malviya, N; Jaffe, I; Ross, J; Hill, A; Belsky, M; Nohria, A; Pimental, S; Rost, J; Thakore, N; Kelleher, A C; Fuligni, G; Chkhikvadze, T; Kaufman, D
INTRODUCTION: Ventilatory ratio (VR) is a bedside index of impaired ventilation that can be used as a surrogate marker for pulmonary dead space fraction (VD/VT). Vasculopathy is hypothesized to increase VD/VT in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. The purpose of this study was to investigate associations between VR and markers of inflammation in critically ill COVID-ARDS patients.
METHOD(S): We conducted a retrospective study of patients admitted to an intensive care unit due to SARS-CoV-2 infection. All subjects required invasive mechanical ventilation and met the Berlin criteria for ARDS. Clinical lab values were collected at two timepoints: 2-8 hours after intubation (T1) and 2-24 hours before tracheostomy (T2). VR was split into high (VR>2) and low (VR< 2) groups. Comparisons were performed using student's t, Mann-Whitney, and z tests for difference in proportions with alpha=0.05.
RESULT(S): Of the 139 subjects enrolled at T1, 67 (48%) had high VR (>2), with an overall mean VR of 2.08. High VR was significantly associated with leukocyte count (WBC) (13.3 vs. 10.6 x10^9/L, p=0.004), and platelet count (284 vs 248 x10^9/L, p=0.003). There was no association between VR status and procalcitonin (p=0.08), d-dimer (p=0.73), fibrinogen (p=0.38), CRP (p=0.22), and ferritin (p=0.33). Since certain markers had non-Gaussian distributions, we determined threshold values. D-dimer over 500 ng/mL was associated with higher VR (2.3 vs. 1.8, p=0.004) and procalcitonin over 0.5 ng/mL was moderately associated with higher VR (2.2 vs 1.9, p=0.052). CRP >181 mug/mL (the median) and ferritin values >1.5x the upper limit of normal were not associated with VR (p=0.30 and p=0.26, respectively). To enrich the dataset, we pooled data from T1 and T2 and treated each as an independent sample. In this pooled analysis, high VR was associated with higher platelet count (282 vs. 253, p=0.046), and higher procalcitonin (3.464 vs. 0.964, p=0.032). There were no significant associations with VR and d-dimer (p=0.88), fibrinogen (p=0.54), CRP (p=0.20), and ferritin (p=0.76) in the pooled data.
CONCLUSION(S): Ventilatory ratio appears to be associated with higher levels of some inflammatory markers including WBC, platelets, d-dimer, and procalcitonin in COVID-ARDS patients
EMBASE:640007247
ISSN: 1530-0293
CID: 5513572

COMPARISON OF THE PROGNOSTIC VALUE OF PULMONARY DEAD SPACE PROXIES IN COVID-19 ARDS OUTCOMES [Meeting Abstract]

Jaffe, I; Malviya, N; Kelleher, A; Fuligni, G; Belsky, M; Ross, J; Rost, J; Thakore, N; Nohria, A; Hill, A; Pimentel, S; Chkhikvadze, T; Kaufman, D
INTRODUCTION: Mortality and morbidity associated with COVID-19 acute respiratory distress syndrome (ARDS) has been associated with pulmonary vasculopathy, which has been hypothesized to increase pulmonary dead space (VD/ VT). However, VD/VT is rarely measured at the bedside. As a result, multiple proxy estimates have been developed. Our hypothesis was proxy estimates for VD/VT would have differing utilities in prognostication of COVID-19 ARDS.
METHOD(S): We conducted a retrospective cohort study of patients admitted to an intensive care unit with SARSCoV- 2 ARDS who required invasive mechanical ventilation. Ventilation parameters were collected 2-8 hours after intubation. The VD/Vt proxies examined were 1) ventilatory ratio (VR), 2) estimation of VD/VT using the Harris-Benedict equation for energy expenditure (VD/VT-HB), 3) direct estimation of VD/VT using Beitler et. al.'s formula (VD/VTDir), and 4) corrected minute ventilation (VECorr). For each proxy, subjects were dichotomized using the median value. Comparisons were performed using the Wilcoxon rank-sum test with alpha=0.05.
RESULT(S): For 139 subjects, mean VR was 2.08 (SD+/-0.80), mean VD/VT-HB was 0.614 (+/-0.15), mean VD/VT-Dir was 0.657 (+/-0.08), and mean VECorr was 12.2 (+/-4.6) L/min. All four proxies had strong inter-measure correlation (Pearson's r 0.748-0.881, p< 0.001 for all comparisons). No proxy was predictive of 30-day hospital mortality. High VR and VECorr were associated with increased morbidity using a composite endpoint of death or organ failure (defined as requiring renal dialysis or extracorporeal membrane oxygenation) with both having an odds ratio of 2.20 (95% CI: 1.12-4.33, p=0.022), while VD/VT-HB (p=0.552) and VD/VT-Dir (p=0.554) were not significantly associated. Of all proxies, only VR was significantly associated with increased sequential organ failure assessment (SOFA) score at 10+/-4 days post-intubation (6.2 vs. 4.8, p=0.024) and more ventilatorfree days within the 30 days after intubation (3.2 vs. 1.8, p=0.029).
CONCLUSION(S): Ventilatory ratio and corrected minute volume appear to have stronger associations with morbidity in COVID-19 ARDS compared to other VD/VT estimates. Ventilatory ratio is also associated with ventilator-free days and delayed SOFA score
EMBASE:640005943
ISSN: 1530-0293
CID: 5513602

VENTILATORY RATIO IDENTIFIES ORGAN FAILURE RISK IN COVID-19 ARDS REQUIRING MECHANICAL VENTILATION [Meeting Abstract]

Jaffe, I; Malviya, N; Chkhikvadze, T; Ross, J; Rost, J; Thakore, N; Kelleher, A; Fuligni, G; Hill, A; Belsky, M; Nohria, A; Pimentel, S; Kaufman, D
INTRODUCTION: Ventilatory ratio (VR) is a simple bedside index of carbon dioxide removal. VR correlates well with physiologic dead space fraction (VD/VT) and clinical outcomes in patients with acute respiratory distress syndrome (ARDS). We hypothesized that high VR would identify COVID-19 ARDS patients with higher risk for death and organ failure.
METHOD(S): We conducted a retrospective cohort study of patients admitted to a single hospital in New York, NY, USA from March-July 2020 who had PCR-confirmed SARS-CoV-2 infection, met the Berlin criteria for ARDS, and required tracheostomy for prolonged invasive mechanical ventilation (MV). MV parameters were collected 2-8 hours after intubation. Based on prior studies, a VR>2 was considered to be abnormally elevated. Comparisons were performed using the Wilcoxon rank-sum test or z-test for difference in proportions with alpha=0.05. The primary outcome was 30- day mortality and the secondary outcome was a composite endpoint of death or organ failure defined as requiring renal replacement or extracorporeal membrane oxygenation (ECMO) during the hospitalization.
RESULT(S): Of 139 subjects enrolled, 67 (48.2%) had a VR>2. Low and high VR groups had similar baseline characteristics, including age (mean 58 years, SD +/-15.2), body mass index (30.1+/-6.69 kg/m2), simplified acute physiology score II (35.4+/-12.4), sequential organ failure assessment (SOFA) score (5.7+/-2.5), and a 19-point review of systemic disease history. High VR was not significantly associated with mortality (OR 0.92, p=0.827). However, high VR was associated with increased risk for the composite endpoint (OR 1.96, p=0.049) and independently identified patients with a higher risk of organ failure (OR 2.03, p=0.047). High VR was also associated with longer hospital length-of-stay for subjects who survived to discharge (52 vs. 43, p=0.035), more MV-free days within the 30 days after intubation (3.2 vs. 1.8, p=0.029), and higher SOFA score at 10+/-4 days post-intubation (6.2 vs. 4.8, p=0.024).
CONCLUSION(S): Ventilatory ratio identifies COVID-ARDS ventilated patients with increased risk for organ failure requiring advanced intervention, as well as patients who may require prolonged mechanical ventilation and hospitalization
EMBASE:640006591
ISSN: 1530-0293
CID: 5513622

A novel Vascular Leak Index identifies sepsis patients with a higher risk for in-hospital death and fluid accumulation

Chandra, Jay; Armengol de la Hoz, Miguel A; Lee, Gwendolyn; Lee, Alexandria; Thoral, Patrick; Elbers, Paul; Lee, Hyung-Chul; Munger, John S; Celi, Leo Anthony; Kaufman, David A
PURPOSE/OBJECTIVE:Sepsis is a leading cause of morbidity and mortality worldwide and is characterized by vascular leak. Treatment for sepsis, specifically intravenous fluids, may worsen deterioration in the context of vascular leak. We therefore sought to quantify vascular leak in sepsis patients to guide fluid resuscitation. METHODS:We performed a retrospective cohort study of sepsis patients in four ICU databases in North America, Europe, and Asia. We developed an intuitive vascular leak index (VLI) and explored the relationship between VLI and in-hospital death and fluid balance using generalized additive models (GAM). RESULTS:Using a GAM, we found that increased VLI is associated with an increased risk of in-hospital death. Patients with a VLI in the highest quartile (Q4), across the four datasets, had a 1.61-2.31 times increased odds of dying in the hospital compared to patients with a VLI in the lowest quartile (Q1). VLI Q2 and Q3 were also associated with increased odds of dying. The relationship between VLI, treated as a continuous variable, and in-hospital death and fluid balance was statistically significant in the three datasets with large sample sizes. Specifically, we observed that as VLI increased, there was increase in the risk for in-hospital death and 36-84 h fluid balance. CONCLUSIONS:Our VLI identifies groups of patients who may be at higher risk for in-hospital death or for fluid accumulation. This relationship persisted in models developed to control for severity of illness and chronic comorbidities.
PMCID:9003991
PMID: 35410278
ISSN: 1466-609x
CID: 5201862

Inhaled pulmonary vasodilators are not associated with improved gas exchange in mechanically ventilated patients with COVID-19: A retrospective cohort study

Lubinsky, Anthony Steven; Brosnahan, Shari B; Lehr, Andrew; Elnadoury, Ola; Hagedorn, Jacklyn; Garimella, Bhaskara; Bender, Michael T; Amoroso, Nancy; Artigas, Antonio; Bos, Lieuwe D J; Kaufman, David
PURPOSE/OBJECTIVE:Measure the effect of inhaled pulmonary vasodilators on gas exchange in mechanically ventilated patients with COVID-19. METHODS:ratio, oxygenation Index (OI), and ventilatory ratio (VR) after initiation of inhaled pulmonary vasodilators. RESULTS:, OI and VR did not significantly change over a five day period starting the day prior to drug initiation in patients who received either iNO or iEPO assessed with a fixed effects model. CONCLUSION/CONCLUSIONS:Inhaled pulmonary vasodilators were not associated with significant improvement in gas exchange in mechanically ventilated patients with COVID-19.
PMCID:8847100
PMID: 35180636
ISSN: 1557-8615
CID: 5163672

Dsi as a predictor of mortality in patients with COVID-19 [Meeting Abstract]

Snavely, C; Ramadan, L; Kozloff, S; Ospina-Tascon, G; Kaufman, D; Bakker, J
INTRODUCTION: In patients with septic shock, the diastolic shock index (DSI), defined as the ratio of heart rate to diastolic blood pressure, has been shown to correlate with mortality. This is thought to be due to the underlying vasodilation and compensatory increases in heart rate. Although infection with COVID-19 frequently presents with sepsis-like symptoms and changes in blood pressure, the role of the DSI in these patients has not been studied. Our study sought to explore if the DSI may be similarly used in patients with COVID-19 to identify individuals with an elevated mortality risk.
METHOD(S): This was an IRB approved retrospective cohort study at a large academic hospital in New York City (NYC). Data was extracted from the electronic medical record by a trained analyst. Inclusion criteria were age 18 or older, admitted from the emergency department (ED) to the intensive care unit (ICU) between 01/01/2020 and 06/30/2020 with a positive test for COVID-19. We excluded individuals who were transferred from the floor or an outside hospital to the ICU and those with incomplete data. Our final cohort included 360 patients from NYC. The heart rate and diastolic blood pressure used to calculate the DSI were based on the first recorded vitals upon presentation to the ED. This was done in conjunction with a study at a University (ICESI) hospital in Cali, Colombia, with a combined cohort of 655 patients.
RESULT(S): The 28-day mortality rate for the combined study population was 24.9%. Descriptive statistics demonstrated a DSI of >= 1.6 was correlated with elevated 28 day mortality. Cox regression controlling for age, body mass index, respiratory rate, and systolic blood pressure, demonstrated that a DSI of >= 1.6 had a hazard ratio of 1.98 (p-value < 0.01, 95% CI 1.40-2.81).
CONCLUSION(S): In our study population, the DSI that correlated with an elevated risk of mortality was considerably lower than was seen in patients with septic shock, underscoring the physiologic differences between patients with septic shock and COVID-19. Further analysis of the data will be aimed at revealing the etiology of these differences
EMBASE:637190498
ISSN: 1530-0293
CID: 5158292

Dead space estimates may not be independently associated with 28-day mortality in COVID-19 ARDS [Meeting Abstract]

Morales-Quinteros, L; Serpa, Neto A; Artigas, A; Blanch, L; Botta, M; Kaufman, D; Schultz, M J; Tsonas, A; Paulus, F; Bos, L
Introduction. Surrogates for impaired ventilation such as estimated dead-spacefractions and the ventilatory ratio have been shown to be independently associatedwith an increased risk of mortality in the acute respiratory distress syndrome and smallcase series of COVID-19 related ARDS. Objectives. Quantify the dynamics and determine the prognostic value of surrogate markers of wastedventilation in patients with COVID-19 related ARDS. Methods. Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVIDis a national, multicenter, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible forparticipation if they had received invasive ventilation for COVID-19 at a participating ICUduring the first month of the national outbreak in the Netherlands. Results. 927 consecutive patients admitted with COVID-19 related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction(by Harris-Benedict and direct method) and ventilatory ratio were significantly higher innonsurvivors than survivors at baseline and during the following days of mechanicalventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors thanin survivors (p < 0.001). As ARDS severity increased, mortality increased with successivetertiles of dead space fraction by Harris-Benedict and by direct estimation, and with anincrease in the VR. The same trend was observed with decreased levels in the tertiles forthe end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that includedchronic comorbidities and ventilation- and oxygenation-parameters, none of the deadspace estimates measured at the start of ventilation or the following days weresignificantly associated with 28-day mortality. Conclusion. There is significant impairment of ventilation in the early course of COVID-19 related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk-model
EMBASE:636288382
ISSN: 2197-425x
CID: 5179312

Fluid Responsiveness and Vasopressor Use in Patients with Septic Shock [Meeting Abstract]

Douglas, I; Alapat, P; Corl, K; Exline, M; Forni, L; Holder, A; Kaufman, D; Khan, A; Levy, M; Martin, G; Sahatjian, J; Seeley, E; Self, W; Weingarten, J; Williams, M; Hansell, D
Introduction. Fluid and vasopressors are central components of septic shock resuscitation but in excess are associated with adverse effects. Dynamic measurement of stroke volume (SV) following a small IV fluid bolus or passive leg raise (PLR) is a safe and feasible method of rapidly predicting the effectiveness of fluid-induced augmentation of cardiac output.The FRESH study demonstrated that SV-guided dynamic assessment could alter the amount of IV fluid administered to patients with septic shock and improve patient outcomes.1The goal of this analysis was to evaluate the use of vasopressors administration in the FRESH patient population. Methods. FRESH was a prospective, randomized global clinical trial among adults with sepsis-associated hypotension comparing PLRguided SV responsiveness (intervention) as a guide for fluid management versus usual care.1 Patients presented to the Emergency Room with sepsis associated hypotension and anticipated ICU admission. In the Intervention arm, patients were assessed for fluid responsiveness before any clinically driven fluid bolus or increase in vasopressors. If the patient's stroke volume increased by 10% or more in response to a passive leg raise (PLR), they were considered fluid responsive and fluid was recommended as the first therapy. If the patient's stroke volume increased by less than 10% during PLR, then the patient was considered not to be fluid responsive and vasopressors were recommended as the first therapy. The protocol included reassessment and therapy as indicated by the PLR result. The control arm received usual care. Results. 83 patients were randomized to the Intervention arm and 41 patients to the Usual Care arm. Patients in the treatment arm received less fluid over the 72 h treatment period (3354.2 +/- 2179.6) compared to the control group (4721.3 +/- 3319.1, p = 0.007) 0.1 A similar number of patients in the treatment and control group were initiated on vasopressors post randomization (25% treatment vs. 20.8% control, p = 0.683). Patients in the treatment group underwent vasopressor use for a similar period of time (40.74 h +/- 51.23 vs 55.64 +/- 87.43 h, reduction of ? 14.91, p = 0.426) Overall, the percentage of PLRs resulting in dose or frequency change in vasopressor was 20%. Conclusion. Physiologically-informed fluid and vasopressor resuscitation using PLR-induced SV change to guide personalized management of septic shock resulted in a lower decreased fluid balance. Although the treatment algorithm directed providers to consider vasopressors when a patient was not fluid responsive, there was no increase in vasopressor administration or increase in time on vasopressors in the treatment group. Administering fluid only when it is effective at improving perfusion (SV change > 10%) may lead to overall more effective perfusion management, and does not increase the need for vasopressors and time on treatment. A personalized approach to fluid management may help improve patient overall patient outcome
EMBASE:636288372
ISSN: 2197-425x
CID: 5179322