Evidence Of Fluid Overload Research Articles

Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites

The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration–response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205′s lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.

LB876 Acute inflammatory edema: A challenging diagnosis in a critically ill patient

A 55-year-old man with a prior history of fibrotic lung disease was admitted to the hospital for bilateral lung transplantation. His post-operational course was complicated by severe volume overload requiring initiation of continuous veno-venous hemodialysis (CVVHD). During this hospitalization, he had developed erythematous plaques over his bilateral thighs. Examination revealed erythematous and edematous plaques with a peau d’orange appearance extending over his bilateral thighs and abdominal pannus. Importantly, the inguinal and infra-abdominal folds were spared. The clinical differential diagnosis included acute inflammatory edema (AIE), early lipodermatosclerosis (LDS), and stasis change. Punch biopsy of a thigh lesion revealed prominent dermal edema, a sparse perivascular and interstitial lymphohistiocytic infiltrate, ectactic vessels, and fibrosis: findings consistent with a diagnosis of AIE. Improvement of the patient’s volume status, increased mobility, and frequent position changes were recommended. AIE is a variant of pseudocellulitis characterized by erythematous and edematous plaques primarily found on the thighs and abdomen that spare areas of increased pressure, such as the inguinal folds. AIE is an acute lymphedema that predominantly affects critically ill patients with hypoalbuminemia, increased body mass index, renal impairment, and evidence of fluid overload. LDS and stasis dermatitis can also present on the thighs and pannus; however, these conditions also commonly manifest on the distal lower extremities and do not spare skin folds. Additionally, LDS and stasis are typically chronic rather than acute. LDS is a lobular panniculitis with fat necrosis, lipomembranous change, and septal fibrosis. In stasis, there are an increased number of thickened capillaries, red blood cell extravasation, and siderophages.

Abstract 183: Diuretic Use In The Emergency Department And Length Of Stay In Patients Hospitalized With Congestive Heart Failure

Background: Among hospitalized heart failure patients with evidence of fluid overload, guidelines recommend prompt use of loop diuretics to reduce morbidity. Little is known about delays in the use of loop diuretics among patients with congestive heart failure admitted from an emergency department (ED). Methods: We identified 2,801 patients admitted via an ED with heart failure at 12 Allina Health hospitals between January 1, 2017 and December 31, 2020. We excluded patients on observational status, no or unknown home loop diuretic dosing, no intravenous (IV) loop diuretic within 24 hours of admission, on home thiazide-like or thiazide-type diuretic and patients who received inotropes or dialysis prior to admission or within 24 hours of admission. Initial diuretic dose was compared to home dose in furosemide equivalents using the Diuretic Strategies in Patients with Acute Decompensated Heart Failure trial logic and categorized into below home dose, equivalent to home dose, or above home dose. We describe patient characteristics and length of stay by category of diuretic use. Results: Among 2801 admitted for heart failure and receiving IV loop diuretics within 24 hours of admission, 1048 (37%) received no IV diuretic in the ED, the initial diuretic dose was below home dose in 346 (12%) patients, equivalent to home dose in 170 (6%) patients, and above home dose in 1237 (44%) patients. Baseline characteristics by category of initial diuretic dose are presented in the Table. Mean length of stay was longest in patients receiving no diuretic in the ED (4.99 days) and shortest in patients receiving a dose above home equivalent (4.48 days) (Table). Conclusions: In a cohort of patients admitted for heart failure, nearly a third of patients failed to receive an IV loop diuretic in the emergency department and this was associated with a longer length of hospital stay. These findings may represent a quality improvement opportunity in the care of patients hospitalized for heart failure.

Patterns Of Renin-Angiotensin-Aldosterone-System Inhibitor Interruption In Patients Hospitalized For Acute Decompensated Heart Failure

Introduction It is unknown if interruption of renin-angiotensin-aldosterone system inhibitors (RAASi) in acute decompensated heart failure (ADHF) impacts future use. Objectives We investigated the frequency and clinical predictors of RAASi interruption in patients with heart failure reduced ejection fraction (EF) during ADHF hospitalization and its impact on chronic therapy. Methods We conducted a retrospective chart review of patients hospitalized for ADHF at our facility with an EF < 40%, on stable RAASi 1 month prior to admission, and evidence of fluid overload. Patient demographics, clinical characteristics, and RAASi use at discharge, 30, and 90 days were compared between patients whose RAASi was continued (RAASi-C) vs interrupted (RAASi-I). Rehospitalizations and death at 30 days were also compared between groups. Results 189 patients were included, mean age was 62±14 years, 53% were male, and 73% were Black. RAASi were interrupted in 56 (30%) patients during the hospital stay. The RAASi-I group had higher serum creatinine (SCr) (2.6 vs 1.5 mg/dL, p=0.003), greater increase in SCr from baseline (0.53 vs 0.01 mg/dL, p=0.001), higher potassium (4.5 vs 4.2 mEq/L, p=0.001), and lower blood pressure (BP) (systolic: 126 vs 138 mmHg, p=0.01; diastolic 73 vs 81mmHg, p=0.007). Logistic regression identified SCr, potassium, and diastolic BP on admission as significant predictors of RAASi interruption. RAASi use at discharge, 30, and 90 days was lower in the RAASi-I group (Table 1). Compared to the RAASi-C group, more patients in the RAASi-I group were re-hospitalized at 30 days (45% vs 27%, p=0.014); deaths at 30 days were similar between groups (3.8% vs 1.8% p=0.486). Conclusions: Increased SCr, higher potassium, and lower diastolic BP are significant predictors of RAASi interruption during an ADHF hospitalization. RAASi interruption was associated with decreased RAASi use through the first 90 days after discharge and higher 30-day rehospitalization. It is unknown if interruption of renin-angiotensin-aldosterone system inhibitors (RAASi) in acute decompensated heart failure (ADHF) impacts future use. We investigated the frequency and clinical predictors of RAASi interruption in patients with heart failure reduced ejection fraction (EF) during ADHF hospitalization and its impact on chronic therapy. We conducted a retrospective chart review of patients hospitalized for ADHF at our facility with an EF < 40%, on stable RAASi 1 month prior to admission, and evidence of fluid overload. Patient demographics, clinical characteristics, and RAASi use at discharge, 30, and 90 days were compared between patients whose RAASi was continued (RAASi-C) vs interrupted (RAASi-I). Rehospitalizations and death at 30 days were also compared between groups. 189 patients were included, mean age was 62±14 years, 53% were male, and 73% were Black. RAASi were interrupted in 56 (30%) patients during the hospital stay. The RAASi-I group had higher serum creatinine (SCr) (2.6 vs 1.5 mg/dL, p=0.003), greater increase in SCr from baseline (0.53 vs 0.01 mg/dL, p=0.001), higher potassium (4.5 vs 4.2 mEq/L, p=0.001), and lower blood pressure (BP) (systolic: 126 vs 138 mmHg, p=0.01; diastolic 73 vs 81mmHg, p=0.007). Logistic regression identified SCr, potassium, and diastolic BP on admission as significant predictors of RAASi interruption. RAASi use at discharge, 30, and 90 days was lower in the RAASi-I group (Table 1). Compared to the RAASi-C group, more patients in the RAASi-I group were re-hospitalized at 30 days (45% vs 27%, p=0.014); deaths at 30 days were similar between groups (3.8% vs 1.8% p=0.486). Conclusions: Increased SCr, higher potassium, and lower diastolic BP are significant predictors of RAASi interruption during an ADHF hospitalization. RAASi interruption was associated with decreased RAASi use through the first 90 days after discharge and higher 30-day rehospitalization.

Antimicrobial Therapy for Pneumonia or Fluid Overload?

Patients with evidence of fluid overload or heart failure (HF) without clinical symptoms of pneumonia are often treated with antimicrobial therapy for pneumonia. We conducted a retrospective study to evaluate the use of antimicrobial therapy in critically ill patients with fluid overload or heart failure diagnosed as pneumonia.A retrospective chart review of patients on antimicrobial therapy treated for pneumonia in the intensive care unit was conducted. The study's primary outcome was the number of cases with no evidence of pneumonia, including fluid overload or heart failure, managed with antimicrobial therapy for pneumonia. Patients on antimicrobial therapy for other infections were excluded. Appropriateness of antimicrobial therapy was based on radiographic evidence, clinical data, and presentation. Patient group categories were A (pneumonia) and B (no evidence of pneumonia, fluid overload, and heart failure). Based on the subdivision of patients in Group B, where there was no evidence of pneumonia, we further classified it into two subgroups: heart failure (HF)/fluid overload (Group B1) and no evidence of HF or fluid overload (Group B2). Patients with evidence of pneumonia (Group A) were compared to the group with fluid overload and heart failure (Group B1). A p-value of < 0.05% was considered significant for detecting statistical difference.Post-screening, data on 56 patients were collected for the study and analyzed. Mean body temperature and white blood cell count were 37.6 + 0.6 oC, and 17.4 + 6.88 x103 µL, respectively. Based on radiographic evidence, clinical data, and presentation, 29 (52%) were classified under Group A, while 27 (48%) were classified under Group B. Median brain natriuretic peptide (BNP) for Group A vs. Group B was 514 (IQR: 1077) vs. 758 (2212) pg/mL p=0.14. The median duration of inpatient antimicrobial therapy was 7 (interquartile range [IQR]: 6) vs. 6 (IQR: 4) days, p=0.52, while the median duration of the total (inpatient and discharge prescription) antimicrobial therapy was 11 (IQR: 6) vs. 11 (IQR: 5), p=0.21. Patients with evidence of pneumonia (Group A) were compared to the group with fluid overload and heart failure (Group B1). The median BNP for the two groups was 514 (IQR: 1077) vs. 1040 (2094) pg/mL, p=0.04. Patients with documented echocardiographic evidence of ejection fraction < 55% were 4 vs. 14 for Groups A and B1, respectively. Additionally, the median BNP for Group A vs. Group B2 was 514 (IQR: 1077) vs. 189 (418) pg/mL, p=0.02.These findings demonstrate a 48% inappropriate use of antimicrobial therapy in patients with congestive heart failure (CHF), or fluid congestion misdiagnosed as pneumonia. There was a significant difference in the median BNP observed in patients with pneumonia compared to those with fluid overload and heart failure treated as pneumonia. More cases of patients with elevated BNP and reduced left ventricular ejection fraction (LVEF) were observed in patients with fluid overload or CHF treated as pneumonia than those diagnosed with pneumonia alone. Appropriate interpretation of radiographic evidence, laboratory data, and critical clinical assessment for the use of empiric antimicrobial therapy in this population is warranted.

Frequency of Transition to Oral Loop Diuretics Prior to Discharge

Introduction Heart failure guidelines recommend that patients with acute decompensated heart failure (ADHF) be transitioned to oral (PO) loop diuretics prior to discharge but little evidence supports this recommendation. Objectives We sought to identify the frequency that patients admitted for ADHF are transitioned to PO loop diuretics prior to discharge, identify predictors for transitioning to PO loop diuretics, and compare outcomes between patients converted to PO loop diuretics (PO group) to those who were not (IV group). Methods We conducted a retrospective chart review of unique adult patients hospitalized for ADHF at our facility between 9/1/2017 and 8/31/2019. Patients hospitalized for ADHF (ICD-10 I50.xx) with evidence of fluid overload, treated with IV loop diuretics during the first 24 hours of admission, and discharged home with a prescription for PO loop diuretic were included. Patients were excluded if they were on dialysis, left against medical advice, received palliative care referral while inpatient, or had a history of cirrhosis or received > 50mg of aldosterone antagonist a day. Patient demographics, clinical features, and practice patterns were characterized to identify predictors of PO transition. Thirty-day readmission rates were compared between the PO and IV groups. Results Among 240 patients included, 155 (65%) patients were transitioned to PO loop diuretics prior to discharge (PO group). Mean age was 63 years, most were men (55%) of African American (66%) descent. Compared to the IV group, the PO group had higher baseline potassium (4.3 vs 4.1 mEq/L, p=0.010), lower eGFR (52 vs 60 mL/min/1.73m2, p=0.016), were less likely to be on hydralazine (12.9% vs 24.7%, p=0.020), and more likely to be on a thiazide-type diuretic (9.7% vs 2.4%, p=0.034) on admission. Neither age, gender, blood pressure, renal function, nor electrolytes were significant predictors of transitioning to PO loop diuretics prior to hospital discharge. Within 30 days, 36 (23.2%) patients in the PO group were rehospitalized compared to 19 (22.4%) patients in the IV group (p=0.88). Conclusions Most patients admitted for ADHF were transitioned to PO loop diuretics prior to discharge. Although differences were noted in baseline characteristics, we did not identify any significant predictors for patients transitioned to PO diuretics. Thirty-day readmission rates were similar between patients who were and were not transitioned. Further study is warranted to identify the best approach for transitioning ADHF patients to PO diuretics prior to discharge.

P1691 A case of congenital pulmonary stenosis

Abstract Introduction We present an unusual case of sequential right ventricular outflow tract obstruction (RVOTO) caused by pulmonary and subpulmonary stenosis, with formation of aortopulmonary collaterals. Case presentation We report a case of a 47 year old Senegalese man who presented with a three year history of shortness of breath on exertion which worsened over the past week. Cardiovascular examination revealed a parasternal heave, a systolic murmur loudest in the pulmonary area and no evidence of fluid overload. A transthoracic echocardiogram revealed leftward septal deviation during systole due to right ventricular pressure overload, severe right ventricular hypertrophy (RV free wall end-diastolic thickness of 8mm) and normal systolic function (FAC 47%), a dilated right atrium and moderate tricuspid regurgitation with estimated maximum pressures of 112mmHg. On continuous-wave doppler of the right ventricular outflow tract (RVOT), there was a late peaking systolic flow with maximum velocity of 3.8m/s. A cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI) was performed which showed sequential stenoses of the RVOT; one at subvalvular level by an infundibular muscular ridge with an area of 0.7 cm2 in mid-systole and one at the level of a dome-shaped pulmonary valve with planimetered valve area of 0.5cm2, severe RV hypertrophy and normal RV ejection fraction. Aortopulmonary collaterals from proximal thoracic descending aorta were seen. The main pulmonary artery was shown to be dilated with no evidence of pulmonary artery branch stenosis. See image: In-plane phase contrast velocity flow mapping of the RVOT using a VENC of 80cm/s, showing aliasing at the level of the pulmonary valve (red arrow) and at the level of the infundibulum (white arrow). Conclusion Congenital pulmonary stenosis (PS) occurs in 8% of congenital heart defects. 80% of pulmonary valve stenosis is typically dome-shaped with commissural fusion whilst the remainder is of the dysplastic type. Congenital PS can be associated with RVOTO at the infundibular level secondary to reactive muscular hypertrophy. In our case, there is a discrete, circumferential muscular ridge at the level of the infundibulum resulting in sequential outflow tract obstruction. PS with intact ventricular septum occurs in conjunction with varying degrees of right ventricular hypertrophy and elevated right ventricular systolic pressures. A dilated pulmonary artery is common in dome-shaped subtype of PS. Survival into adulthood of severe PS is primarily dependent on the adequacy of pulmonary blood flow from systemic-to-pulmonary collateral arteries, which serve as an additive, or the only source of blood supply to the pulmonary arterial vasculature. These collaterals are usually seen in association with cyanotic congenital heart disease such as pulmonary atresia and tetralogy of fallot. Abstract P1691 Figure. Sequential RVOTO

Transfusion-Associated Circulatory Overload: Risks and Prevention

Transfusion-associated circulatory overload (TACO) is one of the leading causes of transfusion associated morbidity and mortality. It occurs in 1 in 5,932 components transfused to 1 in 28,873 components issued in passive haemovigilance systems and 1–11% of patients in active surveillance studies highlighting a significant problem with under-recognition and under-reporting. The International Society of Blood Transfusion definition of TACO is acute or worsening respiratory compromise during or up to 12 hours after transfusion with two or more of the following criteria: evidence of acute worsening pulmonary oedema; evidence of cardiovascular system changes not otherwise explained (tachycardia, hypertension, jugular venous distension, enlarged cardiac silhouette and/or peripheral oedema); evidence of fluid overload; and elevation of B type natriuretic peptide levels to greater than 1.5 times the pre-transfusion value.1 Risk factors include increased age, heart disease or pre-existing heart failure and renal insufficiency.2 The pathophysiology, although likely predominantly due to fluid overload, may also include inflammatory mediators from the transfusion itself. Strategies to mitigate TACO include minimising the volume of transfusion, slowing the rate of transfusion, and potentially the use of diuretics.3 Studies exploring the role of diuretics are underway.

Intravenous rehydration of malnourished children with acute gastroenteritis and severe dehydration: A systematic review.

Background: Rehydration strategies in children with severe acute malnutrition (SAM) and severe dehydration are extremely cautious. The World Health Organization (WHO) SAM guidelines advise strongly against intravenous fluids unless the child is shocked or severely dehydrated and unable to tolerate oral fluids. Otherwise, guidelines recommend oral or nasogastric rehydration using low sodium oral rehydration solutions. There is limited evidence to support these recommendations. Methods: We conducted a systematic review of randomised controlled trials (RCTs) and observational studies on 15 th June 2017 comparing different strategies of rehydration therapy in children with acute gastroenteritis and severe dehydration, specifically relating to intravenous rehydration, using standard search terms. Two authors assessed papers for inclusion. The primary endpoint was evidence of fluid overload. Results: Four studies were identified, all published in English, including 883 children, all of which were conducted in low resource settings. Two were randomised controlled trials and two observational cohort studies, one incorporated assessment of myocardial and haemodynamic function. There was no evidence of fluid overload or other fluid-related adverse events, including children managed on more liberal rehydration protocols. Mortality was high overall, and particularly in children with shock managed on WHO recommendations (day-28 mortality 82%). There was no difference in safety outcomes when different rates of intravenous rehydration were compared. Conclusions: The current 'strong recommendations' for conservative rehydration of children with SAM are not based on emerging evidence. We found no clinical trials providing a direct assessment of the current WHO guidelines, and those that were available suggested that these children have a high mortality and remain fluid depleted on current therapy. Recent studies have reported no evidence of fluid overload or heart failure with more liberal rehydration regimens. Clinical trials are urgently required to inform guidelines on routes and rates of intravenous rehydration therapy for dehydration in children with SAM.

047 COMBINATION OF TENOFOVIR/EMTRICITABINE WITH PROTEASE INHIBITOR - BASED REGIMEN INDUCED ACUTE KIDNEY INJURY REQUIRING HAEMODIALYSIS: A CASE REPORT

Category: Other Presenter: Dr CHUI MUNN ANG Keywords: Human Immunodeficiency Virus, Tenofovir, Protease Inhibitor, Acute Kidney Injury 51 years old with Human Immunodeficiency Virus and Hepatitis C; non compliant to medication, was switched to Tenofovir/Emtricitabine (TDF/FTC) and Lopinavir/ Ritonavir (LPV/r). Renal profile (RP) was normal and urine FEME showed protein 2+ with viral load of 311 748 copies/ml and CD 4 count of 55 cell/ul prior to initiation of therapy. He presented with uraemia after 4 months; normotensive, afebrile with no evidence of fluid overload or infection. Blood parameters showed acute kidney injury with severe metabolic acidosis (ph 7.052, HCO3 9.6mmol/L, urea 48.7mmol/L, creatinine 1771umol/L); Urine showed microscopic haematuria, proteinuria and glycosuria. Ultrasound showed no evidence of obstruction. TDF/FTC and LPV/r were withheld. Regular hemodialysis was only required for 1 month. RP after 3 months showed urea 5.8mmol/L, creatinine 209 umol/L. Renal biopsy showed 33% of focal global glomerulosclerosis with moderate chronic tubulointerstitial damage and acute tubular necrosis. TDF is eliminated by a combination of glomerular filtration and proximal tubular secretion with 20 - 30% of the drug actively transported into renal proximal tubule cells by anion transporters; hence drug interaction of LPV/r with these transporters favours intracellular accumulation and increases risk of renal toxicity (AUC of TDF increased by 32%). The proximal tubular cells injury leads to failure of reabsorption of low molecular weight proteins, glucose, amino acids, phosphate and uric acid; as well as failure of H+ secretion which reflects on the proteinuria, glycosuria, acute kidney injury with renal tubular acidosis requiring renal replacement; supported by evidence of acute tubular necrosis with interstitium occasionally infiltrated by eosinophils from renal biopsy which suggest a case of drug induced nephropathy likely TDF. The combination of TDF/FTC with LPV/r is associated with greater declines in renal function hence patient should be closely monitored to look for any early signs of renal impairment.

Discharge Diuretic Dose and 30-Day Readmission Rate in Acute Decompensated Heart Failure.

Loop diuretics play a crucial role in symptom management in patients with fluid overload. There is a paucity of data regarding optimal diuretic dose at hospital discharge for acute decompensated heart failure (ADHF) patients requiring loop diuretics. To compare all-cause 30-day readmission in ADHF patients on chronic loop diuretics who had an increase in loop diuretic dose at discharge (relative to their preadmission dose) with patients without a change or a decrease in loop diuretic dose at discharge. This was a multicenter, retrospective cohort study. Institutional review board approval was obtained. Patients admitted with a primary discharge diagnosis of heart failure, evidence of fluid overload, and reduced ejection fraction were included. Patients were divided into 2 groups based on total daily loop diuretic dose at discharge: those discharged on an increased dose and those discharged on a dose less than or equal to their preadmission dose. A total of 131 patient admissions met inclusion criteria; 50 had an increase in loop diuretic dose at discharge, and 81 were discharged with no change or a decrease in diuretic dose. Patients in the increased dose group had an all-cause 30-day readmission rate of 20% compared with 38% of patients with no change or a decrease in diuretic dose (adjusted odds ratio = 0.320; 95% CI = 0.117-0.873). In patients admitted for ADHF with reduced ejection fraction and evidence of fluid overload, an increase in loop diuretic dose at discharge was associated with a reduced rate of 30-day hospital readmission.

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Introduction: Transfusion Related Acute Lung Injury (TRALI) is a form of acute lung injury (ALI) seen after exposure to blood products. We present a case of respiratory failure secondary to TRALI in an 18 year old status post scoliosis surgery. We review the medical literature and present diagnostic criteria, pathophysiology and differential diagnosis of TRALI. An 18 year old male with severe spastic quadraparesis and scoliosis with scoliotic curve 80 degrees and restrictive lung disease without prior respiratory requirement was admitted to our pediatric critical care unit (PCCU) status post posterior spinal fusion of T2-S1. Operative course was significant for coagulopathy causing approximate blood loss of 2 liters requiring transfusion of 6 units of packed red blood cells, 4 units of fresh frozen plasma and 2 units of platelets. While in the recovery room his oxygen was easily weaned to a Fi02 of 40%. In the PCCU, he remained intubated and sedated. Three hours after arrival, he developed significant hypoxia with a PaO2/FiO2 ratio of less than 300 suggestive of ALI. His x-ray 4 hours post transfusion revealed diffuse bilateral infiltrates consistent with pulmonary edema and no cardiomegaly. His ventilator requirements significantly increased to a PEEP of 15 and FiO2 of 80% to maintain oxygen saturation above 90%. He remained afebrile and hemodynamics remained stable off vasoactive medications. There were no findings of infection. On post-operative day 2, he tolerated weaning of oxygen. His imaging revealed improvement of pulmonary edema. He was extubated successfully on post-operative day 3 and was transferred to the pediatric floor on postoperative day 4. Our patient met all the criteria for TRALI (acute onset ALI within 6 hours of exposure to blood products, bilateral pulmonary infiltrates and no evidence of fluid overload or cardiogenic pulmonary edema. Given his surgery he fits the two hit theory hypothesized as pathophysiology of TRALI. Non-immune mediated cases are thought to be due to bioreactive lipids and cytokines that accumulate during the storage of blood products. These are referred to as biologic response modifiers (BRM). The non-immune reaction is not caused solely by BRMs. The proposed hypothesis involves a preceding event presensitzing a patient's lungs and leukocytes to this transfusion reaction. This theory is often referred to as the two hit theory. The first hit includes a predisposing event such as infection, a malignancy or a surgery as in our patient above. This first hit activates neutrophils in the pulmonary endothelium. The second hit involves the transfused BRMs causing further neutrophil activation and endothelial damage. The mortality rate from TRALI ranges from 5% to 25%. Most patients recover within 72 hours; as did our patient. However, there have been cases of severe TRALI lasting about 7 days cited in the literature. Morbidity and mortality may be underappreciated because of lack of recognition and underreporting of this diagnosis. Since TRALI is a transient form of ALI, management is usually supportive with mechanical ventilatory support. The pulmonary infiltrates and hypoxemia usually resolve completely without sequelae.

Association between plasma concentration of tolvaptan and urine volume in acute decompensated heart failure patients with fluid overload.

Tolvaptan (TLV) is a useful diuretic for acute decompensated heart failure (ADHF) with fluid overload, but its clinical response varies between patients. The aim of this study is to investigate whether plasma TLV concentrations correlate with the urine volume. ADHF inpatients with evidence of fluid overload and total urine volume < 1,500 mL 24 h after initial intravenous administration of 40 mg furosemide were included in the study. On days 1-7, 7.5 mg oral TLV was added. The plasma TLV concentration, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured on days 1, 3 and 7. In the 52 patients who completed the protocol, the TLV concentration increased significantly from 67.6 ± 30.1 ng/mL on day 1 to 98.3 ± 39.6 ng/mL on day 3 to 144.8 ± 44.2 ng/mL on day 7, and the TLV concentration correlated with total urine volume on days 3 and 7 (r = 0.392, p < 0.01; r = 0.639, p < 0.001, respectively) but not on day 1. The urine volume correlated inversely with PRA and PAC (r = -0.618, p < 0.05; r = -0.547, p < 0.05, respectively). Plasma TLV concentrations correlated with the urine volume in late phase of treatment but not in early phase, which suggests that the effect of TLV may possibly be inhibited by renin-angiotensin-aldosterone system activity.

Body Mass Index and Prognosis in Patients With Chronic Heart Failure

In individuals without known cardiovascular disease, elevated body mass index (BMI) (weight/height2) is associated with an increased risk of death. However, in patients with certain specific chronic diseases, including heart failure, low BMI has been associated with increased mortality. We examined the influence of BMI on prognosis using Cox proportional hazards models in 7599 patients (mean age, 65 years; 35% women) with symptomatic heart failure (New York Heart Association class II to IV) and a broad spectrum of left ventricular ejection fractions (mean, 39%) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. During a median follow-up of 37.7 months, 1831 patients died. After adjustment for potential confounders, compared with patients with BMI between 30 and 34.9, patients in lower BMI categories had a graded increase in the risk of death. The hazard ratios (95% confidence intervals) were 1.22 (1.06 to 1.41), 1.46 (1.24 to 1.71), and 1.69 (1.43 to 2.01) among those with BMI of 25 to 29.9, 22.5 to 24.9, and < 22.5, respectively. The increase in risk of death among patients with BMI > or = 35 was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43). The association between BMI and mortality was not altered by age, smoking status, or left ventricular ejection fraction (P for interaction >0.20). However, lower BMI was associated with a greater risk of all-cause death in patients without edema but not in patients with edema (P for interaction <0.0001). Lower BMI was associated with a greater risk of cardiovascular death and noncardiovascular death. Baseline BMI did not influence the risk of hospitalization for worsening heart failure or due to all causes. In patients with symptomatic heart failure and either reduced or preserved left ventricular systolic function, underweight or low BMI was associated with increased mortality, primarily in patients without evidence of fluid overload (edema).

Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study*

To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients. : Prospective, controlled, randomized study. Thirty-one-bed, mixed medicosurgical department of intensive care. All adult patients with a serum albumin concentration < or =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload. The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group). The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 +/- 1156 vs. 658 +/- 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05). Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.

American College of Cardiology/American Heart Association Chronic Heart Failure Evaluation and Management guidelines: relevance to the geriatric practice.

Heart failure (HF) is the only cardiovascular disease with increasing incidence and prevalence. Most HF patients are older adults. With the aging of the population and effective treatment of hypertension and coronary artery disease, the two major underlying causes of HF, the number of older Americans with HF is expected to rise significantly in the coming decades. HF is the number one hospital discharge diagnosis for older adults. It is one of the causes of frequent hospital readmissions, reflecting acute decompensation and compromised quality of life for patients and increased cost and resource use for the healthcare system. It is also associated with approximately 300,000 deaths annually, most in older adults. Advances in the management of HF in the past several decades have significantly decreased the mortality and morbidity associated with this condition. Randomized controlled trials have demonstrated the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, and spironolactone on survival and quality of life of HF patients, but there is evidence of underuse of evidence-based care for HF. Several national guidelines have been published since 1994 that recommended evidence-based evaluation and management of HF. In 1995, the American College of Cardiologists (ACC) and the American Heart Association (AHA) published their first HF guidelines that recommended left ventricular (LV) function evaluation for all patients presenting with HF and use of ACE inhibitors for all patients with LV systolic dysfunction (LVSD) unless contraindicated. The guidelines recommended the use of hydralazine and isosorbide dinitrate in patients who could not use ACE inhibitors. In addition, digoxin was recommended in patients with HF due to LVSD but not adequately responsive to ACE inhibitors and diuretics and in those with atrial fibrillation and rapid ventricular rates. Diuretic use was recommended for symptomatic patients with evidence of fluid overload. Use of anticoagulation was restricted to patients with atrial fibrillation or to those with a history of systemic or pulmonary embolism. Beta-blockers were reserved for HF patients after acute myocardial infarctions. Recent advances in the management of HF called for a revision of the guidelines. The purpose of revising the 1995 ACC/AHA guidelines was to incorporate recent advances in pharmacological and nonpharmacological approaches to HF treatment and to assist physicians in clinical decision-making in the management of HF. The ACC/AHA invited representatives from the American College of Chest Physicians, the Heart Failure Society of America, the International Society for Heart and Lung Transplantation, the American Academy of Family Physicians, and the American College of Physicians-American Society of Internal Medicine to participate in the preparation of the guidelines. The writing committee searched pertinent medical literature in English using computerized databases such as MEDLINE and EMBASE and manually searching the bibliographies of the selected articles. The writing committee classified HF into four stages, including patients who are at high risk for developing HF. According to this new classification, Stage A and B represent asymptomatic patients, the former at high risk for developing HF but no structural disorder, the latter with structural disorders of the heart. Stage C encompasses patients with underlying structural heart disorders who are symptomatic, either currently or in the past. Stage D includes end-stage HF patients. This new classification is intended to complement the New York Heart Association (NYHA) functional classification of HF into Class I (asymptomatic), Class II (symptomatic on less than ordinary exertion), Class III (symptomatic on ordinary exertion), and Class IV (symptomatic at rest). The recommendations are categorized into those for evaluation and management.

Fluid balance during and after an ironman triathlon.

To record weight changes, fluid intake and changes in serum sodium concentration in ultradistance triathletes. Descriptive research. Ironman triathlon (3.8 km swim, 180 km cycle, 42.2 km run). Air temperature at 1200 h was 21 degrees C, (relative humidity 91%). Water temperature was 20.7 degrees C. 18 triathletes. None. Subjects were weighed and had blood drawn for serum sodium concentration [Na], hemoglobin, and hematocrit, pre-race, post-race, and at 0800 h on the morning following the race ("recovery"); subjects were also weighed at transitions. Fluid intake during the race was estimated by athlete recall. Median weight change during the race = -2.5 kg (p < 0.0006). Subjects lost weight during recovery (median = -1.0 kg) (p < 0.03). Median hourly fluid intake = 716 ml/h (range 421-970). Fluid intakes were higher on the bike than on the run (median 889 versus 632 ml/h, p = 0.03). Median calculated fluid losses cycling were 808 ml/h and running were 1,021 ml/h. No significant difference existed between pre-race and post-race [Na] (median 140 versus 138 mmol/L) or between post-race and recovery [Na] (median 138 versus 137 mmol/L). Plasma volume increased during the race, median + 10.8% (p = 0.0005). There was an inverse relationship between change in [Na] pre-race to post-race and relative weight change (r = -0.68, p = 0.0029). Five subjects developed hyponatremia ([Na] 128-133 mmol/L). Athletes lose 2.5 kg of weight during an ultradistance triathlon. most likely from sources other than fluid loss. Fluid intakes during this event are more modest than that recommended for shorter duration exercise. Plasma volume increases during the ultradistance triathlon. Subjects who developed hyponatremia had evidence of fluid overload despite modest fluid intakes.

Ultrastructural analysis of skeletal muscle

Chronic heart failure (CHF) is characterized by increased systemic vascular resistance and diminished blood flow to exercising skeletal muscle. The pathogenesis of the increased resistance is not known, and may be due to muscle atrophy, functional abnormalities of resistance vessels or to structural changes in the microcirculation such as endothelial cell swelling. We have compared the ultrastructure of the microvasculature in needle biopsies of the quadriceps muscle from seven control subjects with normal left ventricular function to 10 patients with moderate or severe heart failure, optimally treated and without evidence of fluid overload. Samples were processed for ultrathin sectioning using ruthenium red as a specific basement membrane (BM) stain. Electron micrographs were taken of 10 transversely cut capillaries from each specimen. The total cross-sectional area of the vessels and the area of the endothelium was determined, and the short axis diameter was measured as an index of vessel diameter. The BM thickness was calculated from the mean of six readings around the periphery of the vessel. The short axis diameter in the two groups was not significantly different (controls 3.37 +/- 0.21 microns, CHF 3.56 +/- 0.37 microns, mean +/- 1SD). No difference in total cross-sectional area (controls 11.64 +/- 1.86 microns 2, CHF 13.56 +/- 2.78 microns 2) or area of the endothelium (controls 4.90 +/- 1.18 microns 2, CHF 6.00 +/- 1.58 microns 2) was observed. The thickness of the BM was marginally increased in subjects with CHF when compared to control subjects (0.31 +/- 0.077 microns vs 0.246 +/- 0.047 microns, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma renin activity in acute poststreptococcal glomerulonephritis and the haemolytic-uraemic syndrome.

Plasma renin activity (PRA) was determined in 10 children with acute glomerulonephritis and in 10 with the haemolytic-uraemic syndrome (HUS). Low renin levels were found in the hypertensive children with acute nephritis, all of whom had evidence of fluid overload. The amount of this overload correlated directly with the degree of hypertension and inversely with PRA. All the hypertensive children with HUS had high levels of plasma renin, and the highest levels were found in those cases who were subsequently shown to have the more severe degree of renal arteriolar occlusion. The findings emphasize the importance of measures designed to reduce salt and water overloading in the management of hypertension in acute nephritis, while drugs which suppress plasma renin are more likely to control blood pressure in HUS. Estimation of PRA may provide a guide to the management of hypertension in acute renal insufficiency.

Pulmonary edema following blood transfusion reaction.

Severe pulmonary edema was observed in two patients following blood transfusion reactions. The amount of blood transfused was small and there was no evidence of fluid overload in either patient. The roentgenographic appearance is one of bilateral patchy infiltrates suggestive of interstitial edema. Hemolysis of erythrocytes with release of substances causing constriction of pulmonary arterioles or venules, or intravascular coagulation are possible pathophysiologic mechanisms. Therapy consists of the usual respiratory support measures. Dextran 40, heparin sodium, and isoproterenol may be of benefit.