Pulmonary Edema in COVID-19 Treated with Furosemide and Negative Fluid Balance (NEGBAL): A Different and Promising Approach

In COVID-19, pulmonary edema has been attributed to “cytokine storm”. However, it is known that SARS-CoV2 promotes angiotensin-converting enzyme 2 deficit, increases angiotensin II, and this triggers volume overload. Our report is based on COVID-19 patients with tomographic evidence of pulmonary edema and volume overload to whom established a standard treatment with diuretic (furosemide) guided by objectives: Negative Fluid Balance (NEGBAL approach). Retrospective observational study. We reviewed data from medical records: demographic, clinical, laboratory, blood gas, and chest tomography (CT) before and while undergoing NEGBAL, from 20 critically ill patients. Once the NEGBAL strategy was started, no patient required mechanical ventilation. All cases reverted to respiratory failure with NEGBAL, but subsequently two patients died from sepsis and acute myocardial infarction (AMI). The regressive analysis between PaO2/FiO2BAL and NEGBAL demonstrated correlation (p < 0.032). The results comparing the Pao2Fio2 between admission to NEGBAL to NEGBAL day 4, were statistically significant (p < 0.001). We noted between admission to NEGBAL and day 4 improvement in CT score (p < 0.001), decrease in the superior vena cava diameter (p < 0.001) and the decrease of cardiac axis (p < 0.001). Though our study has several limitations, we believe the promising results encourage further investigation of this different pathophysiological approach.

Adjunct Use of Continuous Renal Replacement Therapy with Extracorporeal Membrane Oxygenation Achieves Negative Fluid Balance and Enhances Oxygenation Which Improves Survival in Critically Ill Patients without Kidney Failure

<b><i>Introduction:</i></b> Fluid overload in extracorporeal membrane oxygenation (ECMO) patients has been associated with increased mortality. Patients receiving ECMO and continuous renal replacement therapy (CRRT) who achieve a negative fluid balance have improved survival. Limited data exist on the use of CRRT solely for fluid management in ECMO patients. <b><i>Methods:</i></b> We performed a single-center retrospective review of 19 adult ECMO patients without significant renal dysfunction who received CRRT for fluid management. These patients were compared to a cohort of propensity-matched controls. <b><i>Results:</i></b> After 72 h, the treatment group had a fluid balance of −3840 mL versus + 425 mL (<i>p</i> ≤ 0.05). This lower fluid balance correlated with survival to discharge (odds ratio 2.54, 95% confidence interval 1.10–5.87). Improvement in the ratio of arterial oxygen content to fraction of inspired oxygen was also significantly higher in the CRRT group (102.4 vs. 0.7, <i>p</i> ≤ 0.05). We did not observe any significant difference in renal outcomes. <b><i>Conclusions:</i></b> The use of CRRT for fluid management is effective and, when resulting in negative fluid balance, improves survival in adult ECMO patients without significant renal dysfunction.

High Central Venous Pressure and Right Ventricle Size Are Related to Non-decreased Left Ventricle Stroke Volume After Negative Fluid Balance in Critically Ill Patients: A Single Prospective Observational Study

Background: Optimal adjustment of cardiac preload is essential for improving left ventricle stroke volume (LVSV) and tissue perfusion. Changes in LVSV caused by central venous pressure (CVP) are the most important concerns in the treatment of critically ill patients.Objectives: This study aimed to clarify the changes in LVSV after negative fluid balance in patients with elevated CVP, and to elucidate the relationship between the parameters of right ventricle (RV) filling state and LVSV changes.Methods: This prospective cohort study included patients with high central venous pressure (CVP) (≥8 mmHg) within 24 h of ICU admission in the Critical Medicine Department of Peking Union Medical College Hospital. Patients were classified into two groups based on the LVSV changes after negative fluid balance. The cutoff value was 10%. The hemodynamic and echo parameters of the two groups were recorded at baseline and after negative fluid balance.Results: A total of 71 patients included in this study. Forty in VI Group (LVOT VTI increased ≥10%) and 31 in VNI Group (LVOT VTI increased &lt;10%). Of all patients, 56.3% showed increased LVSV after negative fluid balance. In terms of hemodynamic parameters at T0, patients in VI Group had a higher CVP (p &lt; 0.001) and P(v-a)CO2 (p &lt; 0.001) and lower ScVO2 (p &lt; 0.001) relative to VNI Group, regarding the echo parameters at T0, the RVD/LVD ratio (p &lt; 0.001), DIVC end−expiratory (p &lt; 0.001), and ΔLVOT VTI (p &lt; 0.001) were higher, while T0 LVOT VTI (p &lt; 0.001) was lower, in VI Group patients. The multifactor logistic regression analysis suggested that a high CVP and RVD/LVD ratio ≥0.6 were significant associated with LVSV increase after negative fluid balance in critically patients. The AUC of CVP was 0.894. A CVP &gt;10.5 mmHg provided a sensitivity of 87.5% and a specificity of 77.4%. The AUC of CVP combined with the RVD/LVD ratio ≥0.6 was 0.926, which provided a sensitivity of 92.6% and a specificity of 80.4%.Conclusion: High CVP and RVD/LVD ratio ≥0.6 were significant associated with RV stressed in critically patients. Negative fluid balance will not always lead to a decrease, even an increase, in LVSV in these patients.

Relationship Between Fluid Therapy Strategies and Mortality Among Sepsis Patients in ICU with high CVP: A Retrospective Analysis of the eICU Database

Objective: It is still debated whether sepsis patients with high CVP (central venous pressure) benefit from it. We performed a retrospective study of sepsis patients with CVP ≥ 12 mmHg to analyze mortality resulting from the different amounts of fluid administered in the fluid therapy at the first 6, 24, and 48 h of the course.Methods: This study included sepsis patients from the eICU database who met the sepsis-3 diagnostic criteria and showed CVP ≥ 12 mmHg on admission. We analyzed the differences between the survivors and the non-survivors at baseline and the difference in fluid balance at 6, 24, and 48 h. Restricted cubic spline (RCS) and logistic regression model were used to identify the association between fluid balance and mortality.Results: Out of the 1150 sepsis patients that showed a high CVP obtained from the eICU database, 847 were survivors and 303 were non-survivors. Compared to survivors, non-survivors had a larger positive fluid balance at 6, 24, and 48 h. The fluid balance and mortality in sepsis patients with high CVP showed an inverted U-type relationship. At 6 h, lower mortality was found in patients who required less than -5 ml/kg fluid therapy. At 24 h, mortality was the lowest at -40~-20 ml/kg. At 48 h, low mortality was observed in patients with < -40 ml/kg fluid balance. In septic shock patients with high CVP, positive balance decrease mortality. In sepsis patients with high CVP without a history of chronic heart failure, and with a history of heart failure negative fluid balance can decrease mortality.Conclusion: In the sepsis group without shock, achieving negative fluid balance possible may significantly improve the prognosis of patients with high CVP, and patients with no history of chronic heart failure and patients with history of chronic heart failure should limit fluid infusion. In patients with septic shock whose CVP ≥ 12 mmHg, positive fluid balance may decrease mortality.

What Does SGLT2 Inhibition Add in Managing Hyponatremia Secondary to Syndrome of Inappropriate Antidiuresis (SIAD)?

Background: Apart from treating the underlying causes, other treatment options for SIAD are of limited success. Drug repurposing of SGLT2 inhibitors for use in SIAD has been suggested. Clinical Case: A 72 years old gentleman with type 2 diabetes mellitus, hypertension, ischemic cardiomyopathy (ejection fraction 40%) and paranoid personality disorder presented with 3-day history of confusion, vomiting and reduced appetite. On examination, he was fully alert, afebrile, blood pressure 173/81 mmHg, heart rate 83 beats per minute and euvolemic. There were fine crackles in the lung bases bilaterally. Random capillary blood glucose level was 5.6 mmol/L (100 mg/dL) and there was no hypoxia. Laboratory results were suggestive of SIAD (serum sodium [Na] 115 mmol/L, serum osmolality 241 mmol/kg, urine osmolarity 458 mmol/kg, spot urine Na 56.7 mmol/L) with normal fT4 (17.6 pmol/L [1.37 ng/dL]), TSH (1.6 mIU/L) and cortisol (821 nmol/L [29.7 mcg/dL]) levels. Medications at admission were daily dosing of olanzapine 7.5 mg, sitagliptin/metformin 50/850 mg, losartan 50 mg, rosuvastatin 10 mg and aspirin 100 mg. Further investigations for causes of SIAD including magnetic resonance imaging of the brain and contrast-enhanced computed tomography of thorax, abdomen and pelvis were normal. He was treated with fluid restriction (1 liter/day) and furosemide (oral 20 mg daily for 2 doses, followed by intravenous 20 mg twice daily for 3 doses) on day 1-4, leading to negative fluid balance (total 3300 ml) with an increment in serum Na to 124 mmol/L on day 5. However, this was accompanied by a reduction in systolic blood pressure (148 to 118 mmHg) and serum potassium level (4.7 to 3.7 mmol/L), along with marked increases in urea (2.7 to 8.8 mmol/L) and creatinine levels (51 to 75 µmol/L) (eGFR from &gt;90 to 87 mL/min/1.73m2). Hence, furosemide was stopped and empagliflozin 12.5 mg daily was initiated on day 5 with continuation of fluid restriction. Serum Na level increased by 2 mmol/L to 126 mmol/L after 12 hours and by 3 mmol/L (to 129 mmol/L) on subsequent day with negative fluid balance (950 ml per 24 hours). Urea and eGFR levels improved and losartan was reintroduced for blood pressure control. There was no euglycemic diabetic ketoacidosis episode. Patient was discharged on day 10 with a serum Na level of 131 mmol/L. Outpatient follow up 5 days after discharge showed further improvement in serum Na level to 134 mmol/L with serum osmolality 286 mmol/kg and urine osmolarity 672 mmol/kg. Clinical Lesson: SGLT2 inhibition can be considered as one of the treatment options of hyponatremia secondary to SIAD with good tolerability

Application and outcomes of extracorporeal life support in emergency general surgery and trauma

Background: We analyzed the use of Extracorporeal Membranous Oxygenation (ECMO) in acute care surgery patients at our Level-1 trauma center. We hypothesized that this patient population has improved ECMO outcomes. Methods: This was a retrospective analysis of emergency general surgery and trauma patients placed on ECMO between the periods of October 2013 and February 2020. There were 10 surgical and 12 trauma patients studied, who eventually required ECMO support. ECMO support and ECMO type/modality were analyzed with injury and survival prognostic scores examined. Main results: Overall, 16 of the 22 patients survived to hospital discharge, for a survival rate of 73%. Mean age was 34.18 years. Mean hospital length of stay was 23.4 days with mean days on ECMO equal to 7.5. The net negative fluid balance was 5.36 L. Conclusions: The survival of our ECMO cohort is notably higher than previously cited studies. Our group demonstrated decreased length of time on ECMO, decreased length of stay in the hospital, and similar rates of complications compared to prior reports. ECMO is a useful modality in acute care surgical patients and should be considered in these patient populations. Our focus on net negative fluid balance for ECMO patients demonstrates improved survival. ECMO should be considered early in surgical patients and early in advanced trauma life support.

High Central Venous Pressure and Right Ventricle Size are Related to Increased Stroke Volume to Negative Fluid Balance in Critically Ill Patients

BackgroundThis study aimed to determine whether a negative fluid balance can increase stroke volume (SV) and the relationship between changes in hemodynamics variables.MethodsThis prospective study included patients with high central venous pressure (CVP) (≥8 mmHg) treated in the Critical Medicine Department of Peking Union Medical College Hospital. Patients were classified into two groups based on their right to left ventricle diastolic dimension (RVD/LVD) ratio using a cutoff value of 0.6. The hemodynamic and echo parameters of the two groups were recorded at baseline and after negative fluid balance. ResultsThis study included 71 patients: 35 in Group 1 (RVD/LVD≥ 0.6) and 36 in Group 2 (RVD/LVD <0.6). Of all patients, 56.3% showed increased SV after negative fluid balance. Cox logistic regression analysis suggested that a high CVP and RVD/LVD ratio were significant independent risk factors for SV increase after negative fluid balance in critically patients without underlying cardiac disease. The AUC of CVP was 0.894. A CVP> 10.5 mmHg provided a sensitivity of 87.5% and a specificity of 77.4%. The AUC of CVP combined with the RVD/LVD ratio was 0.926 ,which provided a sensitivity of 92.6% and a specificity of 80.4%. ConclusionHigh CVP and RVD/LVD ratio were identified as independent risk factors for RV volume overload in critically patients without underlying cardiac disease. A reduced intravascular volume may increase SV for these patients.

Passive Peritoneal Drainage Impact on Fluid Balance and Inflammatory Mediators: A Randomized Pilot Study

Background: Infants after cardiopulmonary bypass are exposed to increasing inflammatory mediator release and are at risk of developing fluid overload. The aim of this pilot study was to evaluate the impact of passive peritoneal drainage on achieving negative fluid balance and its ability to dispose of inflammatory cytokines. Methods: From September 2014 to November 2016, infants undergoing STAT category 3, 4, and 5 operations were randomized to receive or not receive intraoperative prophylactic peritoneal drain. We analyzed time to negative fluid balance and perioperative variables for each group. Pro- and anti-inflammatory cytokines were measured from serum and peritoneal fluid in the passive peritoneal drainage group and serum in the control group postoperatively. Results: Infants were randomized to prophylactic passive peritoneal drain group (n = 13) and control (n = 12). The groups were not significantly different in pre- and postoperative peak lactate levels, postoperative length of stay, and mortality. Peritoneal drain patients reached time to negative fluid balance at a median of 1.42 days (interquartile range [IQR]: 1.00-2.91), whereas the control at 3.08 (IQR: 1.67-3.88; P = .043). Peritoneal drain patients had lower diuretic index at 72 hours, median of 2.86 (IQR: 1.21-4.94) versus 6.27 (IQR: 4.75-11.11; P = .006). Consistently, tumor necrosis factor-α, interleukin (IL)-4, IL-6, IL-8, IL-10, and interferon-γ were present at higher levels in peritoneal fluid than serum at 24 and 72 hours. However, serum cytokine levels in peritoneal drain and control group, at 24 and 72 hours postoperatively, did not differ significantly. Conclusions: The prophylactic passive peritoneal drain patients reached negative fluid balance earlier and used less diuretic in early postoperative period. The serum cytokine levels did not differ significantly between groups at 24 and 72 hours postoperatively. However, there was no significant difference in mortality and postoperative length of stay.