Furosemide Administration Research Articles

The dynamics of urine sodium concentration after intra-venous furosemide in patients with acute heart failure

Abstract Background The urine sodium concentration measured at 2 hours after the administration of intravenous (IV) furosemide in patients with acute heart failure (AHF) is recommended as a marker to assess the responsiveness to IV furosemide. However, little is known regarding the dynamics of natriuresis in the very acute phase after IV furosemide and its association with prognosis in patients with AHF. Purpose The aim of this study is to investigate the dynamics of natriuresis in the very acute phase after IV furosemide and its prognostic implication in patients with AHF. Methods DIURESIS-AHF (Diuretic Resistance Measured by Sodium Excretion and Urine Output in Acute Heart Failure) is a multicenter, prospective, and observational study that evaluated the urine samples at the time of 0h, 1h, 2h, 6h, and 24h after the first administration of IV furosemide in hospitalized patients with AHF. Results After excluding 20 patients who needed additional IV furosemide within the first 6 hours, and 9 patients with missing data about 1h-spot urine sample, 84 patients with AHF (79±8 years, 55% men) were analyzed. Median N-terminal pro-brain natriuretic peptide levels at admission were 4722 [interquartile: 2616-8095] pg/mL, and median first IV furosemide doses were 20 [interquartile:20-20] mg. 29 combined event of all-cause death and heart failure rehospitalization were observed during a 1-year follow-up after registration. Urine sodium concentration corrected for urine creatinine concentration peaked 1 hour and decreased at 2 hours after IV furosemide. Kaplan-Meier curve analysis indicated that 1h urine sodium concentration below 50 mEq/L was significantly associated with a high incidence of composite endpoint (Log-rank P=0.033), and this association was retained even after adjusting for age and sex (hazard ratio, 2.37 [95% CI, 1.03-5.45]; P=0.042), but 2h urine sodium below 50 mEq/L was not associated with a poor prognosis (Log-rank; P=0.630). Conclusions Urinary sodium excretion after IV furosemide administration peaked at 1 hour after IV furosemide and decreased at 2 hours in patients with AHF. The urine sodium concentration below 50 mEq/L at 1 hour, but not 2 hours, was associated with adverse events.Urine Na trajectoriesKaplan Meier curves

Effect of furosemide on comprehensive renin-angiotensin-aldosterone system activity of Thoroughbred horses.

Furosemide, a commonly used diuretic, activates the renin-angiotensin-aldosterone system (RAAS) in other species. Little is known about RAAS peptide activation in horses. To evaluate equilibrium analysis as a practical method for RAAS quantification in horses and describe the RAAS response to a single dose of furosemide. We hypothesize that furosemide would cause transient increase in RAAS peptides in horses. 14 healthy adult thoroughbreds from a university teaching herd. Horses received either furosemide (1 mg/kg IV) or saline IV in a crossover study design. Protease-inhibited samples were compared with equilibrium analysis samples with Deming regression analysis. Renin-angiotensin-aldosterone system hormones were evaluated at 0, 0.25, 0.5, 4, and 24 hours postadministration, via equilibrium analysis. Values were compared with a mixed effects model. Correlation between protease inhibition and equilibrium analysis was high for angiotensin I peptide (AngI) and angiotensin II peptide (AngII) (r = .92 and .95, respectively). Baseline RAAS peptide concentrations were below the limit of detection except AngII (median, 7.5 [range, 3.5-14.0] pmol/L). Furosemide administration resulted in an increase in AngI (8.0 [0.5-15.5] pmol/L, P = .03), AngII (33.7 [9.6-57.9] pmol/L, P = .0008), angiotensin III peptide (AngIII) (2.9 [0.9-4.9] pmol/L, P = .0005), angiotensin IV peptide (AngIV) (2.0 [0.6-3.4] pmol/L, P = .0005), and angiotensin 1-5 peptide (Ang1-5) (5.6 [1.2-5.9] pmol/L, P = .003) at 4 hours. Differences are reported as difference in the mean (95% confidence interval [CI]). Furosemide produced an increase in hormones associated with both the classical and alternative RAAS pathways. Serum equilibrium analysis is practical for RAAS analysis in horses.

Ramucirumab-induced ascites with endothelial growth factor receptor mutation-positive non-small cell lung cancer: Two case reports.

Ramucirumab (RAM) has been approved for the treatment of non-small cell lung cancer (NSCLC). Here, we report two cases of RAM-induced ascites with epidermal growth factor receptor-mutant NSCLC. Patient 1, a 72-year-old man, developed ascites 20 months after erlotinib (ERL) and RAM administration, which resolved after their discontinuation and performing paracentesis. Patient 2, an 83-year-old woman, developed ascites 9 months after ERL and RAM administration, which resolved after RAM discontinuation and furosemide administration. Ramucirumab administration can cause ascites due to increased hepatic sinusoidal pressure. Clinicians should be aware of RAM-induced ascites in patients with NSCLC and should appropriately manage it.

Effect of maneuvers, diuresis, and fluid administration on ultrasound-measured liver stiffness after Fontan.

To determine the effect of stress maneuvers/interventions on ultrasound liver stiffness measurements (LSMs) in patients with Fontan circulation and healthy controls. In this prospective, IRB-approved study of 10 patients after Fontan palliation and 10 healthy controls, ultrasound 2D shear-wave elastography LSMs were acquired at baseline and after maximum inspiration, expiration, standing, handgrip, aerobic exercise, i.v. fluid (500mL normal saline) administration, and i.v. furosemide (20mg) administration. Absolute and percent change in LSM were compared between baseline and each maneuver, and then from fluid infusion to after diuresis. Median ages were 25.5 and 26 years in the post-Fontan and control groups (p = 0.796). LSMs after Fontan were higher at baseline (2.6 vs. 1.3m/s) and with all maneuvers compared to controls (all p < 0.001). Changes in LSM with maneuvers, exercise, fluid, or diuresis were not significant when compared to baseline in post-Fontan patients. LSM in controls increased with inspiration (+0.02m/s, 1.6%, p = 0.03), standing (+0.07m/s, 5.5%, p = 0.03), and fluid administration (+0.10m/s, 7.8%, p = 0.002), and decreased 60 minutes after diuretic administration (-0.05m/s, -3.9%, p = 0.01) compared to baseline. LSM after diuretic administration significantly decreased when compared to after i.v. fluid administration at 30 minutes (-0.79m/s, -26.5%, p = 0.004) and 60 minutes (-0.78m/s, -26.2%, p = 0.017) for patients after Fontan and controls at 15 minutes (-0.12m/s, -8.70%, p = 0.002), 30 minutes (-0.15m/s, -10.9%, p = 0.003), and 60 minutes (-0.1m/s, -10.9%, p = 0.005). LSM after Fontan is higher with more variability compared to controls. Diuresis is associated with significantly decreased liver stiffness in both patients after Fontan and controls, with the suggestion of a greater effect in Fontan patients.

A Novel Index for Survival in Acute Heart Failure: Diuretic Efficiency Score

Aims: Acute heart failure (AHF) is the leading cause of hospital admissions among adults ≥65. Loop diuretics are the mainstay of treatment of congestion in AHF. Response to loop diuretics is closely related to morbidity and mortality. In this study, we aimed to investigate (1) the clinical determinants of diuretic efficiency (DE) by using three separate indicators for assessing DE and (2) the prognostic effect of diuretic efficiency in acutely decompensated heart failure patients. Methods: 42 consecutive patients admitted to the hospital for acutely decompensated heart failure were included. Early diuretic response, spot urine sodium excretion (UNa), and hemoconcentration were evaluated individually to predict loop diuretic efficiency. Results: Good early diuretic response (EDR) was associated with higher diastolic blood pressure on admission and eGFR, atrial fibrillation, and bolus dosing of intravenous furosemide. Hypertension and low systolic blood pressure on admission were inversely related to hemoconcentration. Conclusion: Diuretic efficiency is strongly influenced by the heart rhythm, renal function, blood pressure, prevalence of hypertension, and schedule of furosemide administration. We developed a novel, 3-variable index called DES (diuretic efficiency score) that predicts mortality in AHF patients. Future research in larger cohorts is needed to validate DES as a predictor of mortality in heart failure.

Assessment of ureteric jets as a supportive diagnostic modality for unilateral pelvi-ureteric junction obstruction and its utility in follow-up: A pilot study

Pelvi-Ureteric Junction Obstruction (PUJO) is a common cause of hydronephrosis (HDN) in children. While ultrasonography (USG) is useful for initial assessment and grading of hydronephrosis, it cannot differentiate obstructive from non-obstructive cases. Renal Dynamic Scintigraphy (RDS) confirms the diagnosis but involves ionizing radiation exposure. Ureteric jets using colour Doppler USG have been proposed for diagnosing obstructive HDN. Our study aimed to evaluate Ureteric Jet Frequency (UJF) and Relative Jet Frequency (RJF) in unilateral PUJO before and after furosemide (Lasix) administration, assessing their diagnostic and post-operative utility. Children (<14 years) with unilateral HDN underwent USG and RDS for PUJO diagnosis. Pyeloplasty was performed based on standard criteria. UJF and RJF were assessed before and after furosemide administration (0.5mg/kg) by colour Doppler USG. The non-obstructed side was taken as the control. Follow-up included repeat RDS and ureteric jet assessment. Fifty-two cases were included. UJF (pre- and post-Lasix) was significantly lower in the obstructed side compared to the non-obstructed side at baseline and post-pyeloplasty (p<0.0001). However, the baseline UJF difference between cases and controls was not significant (p>0.05). UJF and RJF (pre- and post-Lasix) increased postoperatively. The UJF difference decreased postoperatively (p<0.05). (attached Table) CONCLUSION: UJF and RJF are useful for diagnosing and monitoring unilateral PUJO. The effect of furosemide on UJF needs to be assessed using additional studies with larger sample sizes to understand if it can affect UJF in a way similar to that noted in diuretic scintigraphy.

Perioperative optic nerve sheath diameter variations in patients with end-stage renal failure undergoing robotic-assisted kidney transplant: a prospective observational study.

Patients with chronic kidney disease (CKD) who undergo hemodialysis are predisposed to interstitial cerebral edema. Robotic-assisted laparoscopic surgery can increase optic nerve sheath diameter (ONSD) and intracranial pressure. The impact of robotic-assisted kidney transplant (RAKT) on ONSD is complicated by the presence of CKD, the administration of furosemide and mannitol, and the manipulation of hemodynamics. We examined ONSD variations in patients undergoing RAKT over a 1-year period at our institution. Furthermore, we attempted to identify any perioperative hemodynamic factors influencing these changes. This prospective study included 20 patients undergoing RAKT. ONSD, heart rate, central venous pressure, systolic blood pressure, diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured following intubation (T1), after assuming the steep Trendelenburg position (T2), 1 hour after docking (T3), upon reperfusion (T4), after transition to the supine position (T5), and 3 hours postextubation (T6). Repeated measures analysis of variance with post hoc Bonferroni correction was employed to compare variables at each time point. Pearson correlation analysis was utilized to assess relationships between variables. P-values ≤0.05 were considered to indicate statistical significance. ONSD (in mm) increased from T1 (3.60±0.44) to T3 (4.06±0.45, P=0.002) and T4 (3.99±0.62, P=0.046), before falling to its lowest value at T6 (3.42±0.64, P=0.002). Pearson correlation analysis revealed significant correlations (P<0.05) between changes in ONSD at T3 and both DBP (r=0.637) and MAP (r=0.522). During RAKT with open ureteric anastomosis, ONSD initially increased, then decreased following reperfusion. DBP and MAP displayed positive correlations with ONSD changes at T3.

Human Factors Validation of a Wearable, On-Body Infusor for Subcutaneous Administration of Furosemide.

Furoscix® (subcutaneous furosemide) is administered using a wearable On-Body Infusor (OBI) and is approved for the treatment of congestion associated with heart failure (HF). The purpose of this study was to assess the safe and effective use of the OBI and Instructions for Use (IFU) by patients with HF, caregivers, and healthcare practitioners (HCPs). Sixty participants (patients, n=30; caregivers, n=15; HCPs, n=15) were evaluated on completion of OBI use tasks and IFU knowledge tasks in a simulated use environment. Fifteen of the patients received OBI/IFU training before evaluation. Overall, 893/900 (99.2%) use tasks and 2211/2220 (99.6%) knowledge tasks were completed successfully, without differences due to training. The most common (n=6) use error was failure to wipe skin or cartridge tip with an alcohol wipe. Errors were due to forgetfulness/misinterpretation rather than IFU clarity. The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.

#1651 Urinary oxygen partial pressure: closely associated with hourly urine output induced by furosemide in patients with acute renal injury

Abstract Background and Aims Urine oxygen level, an indicator of kidney medullar oxygenation, is promising for predicting the onset of acute kidney injury (AKI). Furosemide, a commonly used diuretic in ICU, significantly increases urine output and is believed to change kidney medullar oxygenation. We monitored the longitudinal change of urinary oxygen partial pressure during bolus or pump administration of furosemide, aiming to describe the reaction pattern in an AKI-susceptible patient population. Method The prospective observational pilot study included seven adult patients in the ICU because of cardiac surgery or sepsis. We monitored the continuous urinary oxygen partial pressure for 8-24 hours through a device placed between the urinary catheter and collecting bag during furosemide administration, recorded hourly urine output simultaneously from a urine bag, and followed the patients in the hospital for the onset and development of AKI. Results We recruited three female patients and four male patients with an average age of 54 years and a medium of 5 days in ICU with an AKIN stage I of AKI during their hospital stay. None of them developed more severe stage AKI or required any kidney replacement therapy. We found a reverse correlation pattern between hourly urine output and urinary oxygen partial pressure. Specifically, the urine oxygen level dropped during urine volume increase caused by furosemide bolus administration and abolished by furosemide administration through a pump with more stable urine output. The paired t-test showed a significant increase in average urine oxygen level (mean difference = 21.2 mmHg, p = 0.044) recorded during the “high hourly urine output” period compared to the “low hourly urine period”. Conclusion We first found a drop in urinary oxygen partial pressure during the high urine output period elicited by bolus furosemide administration. It shed light on the confounding factors in AKI predicating during possible furosemide administration.

Furosemide and Ductus Arteriosus Closure in Very-Low-Birth-Weight Preterm Infants: A Comprehensive Retrospective Study.

Ductus arteriosus closure may be delayed in preterm infants, and prostaglandin, a vasodilator, can affect ductal patency. Furosemide can increase renal prostaglandin synthesis, so its net effect on patent ductus arteriosus (PDA) is uncertain. Our goal is to explore the relationship between furosemide and spontaneous ductal closure in very-low-birth-weight preterm infants. Our treatment for PDA involves fluid restriction initially and furosemide administration for hemodynamically significant PDA until closure is confirmed by the echocardiogram. We enrolled 105 infants from 1 January 2019 to 30 June 2022 and evaluated the impact of furosemide on ductal closure, including exposure duration and cumulative dose. There is no correlation between furosemide exposure and spontaneous ductal closure (p = 0.384). Furosemide exposure does not delay the postmenstrual age at which spontaneous ductal closure occurs (p = 0.558). The time for spontaneous ductal closure is positively associated with furosemide prescription days (coefficient value = 0.547, p = 0.026) and negatively with gestational age (coefficient value = -0.384, p = 0.062). The prescription of furosemide does not impact the probability or time duration of ductus arteriosus spontaneous closure. The cumulative dose of furosemide has minimal impact on ductal closure. The correlation between furosemide exposure duration and ductal patency duration is likely due to our treatment protocol, with gestational age being a significant factor.

Diuresis Efficacy in Ambulatory Congested Heart Failure Patients: Intrapatient Comparison of 3 Diuretic Regimens (DEA-HF)

BackgroundLimited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients. ObjectivesThe authors sought to compare the potency and safety of commonly used diuretic regimens in CHF patients. MethodsA prospective, randomized, open-label, crossover study conducted in NYHA functional class II to IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250 mg; IV furosemide 250 mg plus oral metolazone 5 mg; and IV furosemide 250 mg plus IV acetazolamide 500 mg. Treatments were administered once a week, in 1 of 6 randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation. ResultsA total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4,691 mg (95% CI: 4,153-5,229 mg) compared with furosemide alone, 3,835 mg (95% CI: 3,279-4,392 mg; P = 0.015) and to furosemide plus acetazolamide 3,584 mg (95% CI: 3,020-4,148 mg; P = 0.001). Furosemide plus metolazone resulted in 1.84 L of urine (95% CI: 1.63-2.05 L), compared with 1.58 L (95% CI: 1.37-1.8); P = 0.039 collected following administration of furosemide plus acetazolamide and 1.71 L (95% CI: 1.49-1.93 L) following furosemide alone. The incidence of worsening renal function was significantly higher when adding metolazone (39%) to furosemide compared with furosemide alone (16%) and to furosemide plus acetazolamide (2.6%) (P < 0.001). ConclusionsIn ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared with IV furosemide alone or furosemide plus acetazolamide.

Reduced congestion and improved response to a fluid/sodium challenge in chronic heart failure patients after initiation of sacubitril/valsartan: The NATRIUM-HF study.

The effects of initiating sacubitril/valsartan in patients with stable heart failure with reduced ejection fraction (HFrEF) on response to fluid and sodium expansion are unknown. We have explored changes in natriuresis, diuresis, and congestion in response to the administration of intravenous fluid/sodium load in patients with HFrEF before as compared to after the initiation of sacubitril/valsartan. At baseline (before sacubitril/valsartan initiation) and 2 and 3 months after the initiation, patients underwent an evaluation that consisted of three phases of 3 h: the rest phase (0-3 h), the load phase (3-6 h) in which 1 L of intravenous Ringer solution was administered, and the diuretic phase (6-9 h) at the beginning of which furosemide was administered. Overall, 216 patients completed the study. In comparison to baseline values, at 2 and 3 months after sacubitril/valsartan initiation, patients' diuresis and natriuresis in response to Ringer administration significantly increased (mean difference: 38.8 [17.38] ml, p = 0.0040, and 9.6 [2.02] mmol, p < 0.0001, respectively). Symptoms and signs of congestion after the fluid/sodium challenge were significantly decreased at months 2 and 3 compared to baseline. Compared to baseline, there was also an increment of natriuresis after furosemide administration on sacubitril/valsartan (9.8 [5.13] mmol, p = 0.0167). There was a significant decrease in body weight in subsequent visits when compared to baseline values (-0.50 [-12.7, 7.4] kg at 2 months, and -0.75 [-15.9, 7.5] kg at 3 months; both p < 0.0001). The initiation of sacubitril/valsartan in HFrEF patients was associated with improvements in natriuresis, diuresis, and weight loss and better clinical adaptation to potentially decongestive stressors.

Evaluation of renal sodium handling in heart failure with preserved ejection fraction: A pilot study.

The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.

Uncontrolled hypertension and hypertensive urgency: One-year single-center emergency department experience.

The prevalence of uncontrolled hypertension remains a significant concern in public healthcare systems, including daily practices of emergency departments (ED). We aimed to characterize patients admitted to an ED for elevated blood pressure (BP) and to identify factors leading to hospitalization. This retrospective analysis included all patients admitted to an ED in a tertiary hospital in 2022 due to an acute BP rise without hypertensive emergencies. The studied group (n = 570) constituted 1.5% of all ED admissions in 2022. The median age was 67 years (Q1-Q3) (52-75), 68.9% were females. Systolic BP (200 mm Hg [180-212]) and diastolic BP (105 mm Hg [100-115]) at home were higher than during triage (173 mm Hg [160-190] and 95 mm Hg [84-103], respectively [P <0.0001]). Thirty-nine percent of the studied population had taken BP-lowering agents before ED admission (captopril in 91.8% of cases). In the ED, nitrendipine (54.2%), captopril (38.1%), furosemide (16.3%), urapidil (10.0%), and nitroglycerine (1.9%) were administered. Eventually, a median of 140/82 mm Hg BP was reached in the median time of 288 minutes (202-400). Hospitalization was necessary in 5.4% of patients. The need for furosemide or urapidil administration in the ED doubled the risk of hospitalization (OR, 2.0; P <0.01). Before ED admission, only 17.0% of patients received guidelines-recommended single-pill combination therapy, and 17.6% had already visited ED for uncontrolled hypertension (median of 388 days earlier). Elevated BP is a common reason for admission to the ED. Crucially, improvements in long-term hypertension treatment and education are needed to reduce the number of patients seeking ED care for elevated BP.

Hemodynamic Changes in Intrarenal Blood Flow are Associated With Poor Prognosis in Patients With Acute Decompensated Heart Failure.

To evaluate a potential role of different patterns of intrarenal blood flow using Doppler ultrasound as a part of determining the severity of venous congestion, predicting impairment of renal function and an unfavorable prognosis in patients with acute decompensated chronic heart failure (ADCHF). This prospective observational single-site study included 75 patients admitted in the intensive care unit for ADCHF. Upon admission all patients underwent bedside renal venous Doppler ultrasound to determine the blood flow pattern (continuous, biphasic, monophasic). In one hour after the initiation of intravenous diuretic therapy, sodium concentration was measured in a urine sample. The primary endpoint was the development of acute kidney injury (AKI). The secondary endpoints were the development of diuretic resistance (a need to increase the furosemide daily dose by more than 2 times compared with the baseline), decreased natriuretic response (defined as urine sodium concentration less than 50-70 mmol/l), and in-hospital death. According to the data of Doppler ultrasound, normal renal blood flow was observed in 40 (53%) patients, biphasic in 21 (28%) patients, and monophasic in 14 (19%) patients. The monophasic pattern of intrarenal blood flow was associated with the highest incidence of AKI: among 14 patients in this group, AKI developed in 100% of cases (OR 3.8, 95% CI: 2.5-5.8, p&lt;0.01), while among patients with normal and moderate impairment of renal blood flow, there was no significant increase in the risk of developing AKI. The odds of in-hospital death were increased 25.77 times in patients with monophasic renal blood flow (95% CI: 5.35-123.99, p&lt;0.001). Patients with a monophasic intrarenal blood flow pattern were also more likely to develop diuretic resistance compared to patients with other blood flow patterns (p&lt;0.001) and had a decreased sodium concentration to less than 50 mmol/l (p&lt;0.001) in a spot urine test obtained one hour after the initiation of furosemide administration. Patients with monophasic intrarenal blood flow are at a higher risk of developing AKI, diuretic resistance with decreased natriuretic response, and in-hospital death.

Respiratory emergencies in adult horses

SummaryAlthough respiratory distress is encountered infrequently in equine practice, it can be serious and potentially fatal, requiring immediate and decisive intervention. History and physical examination can often give sufficient clues to identify the cause of respiratory distress and initiate emergency treatment. Ultrasonography can also be invaluable when assessing distress caused by lower respiratory tract issues. Upper respiratory tract obstruction, tension pneumothorax and occasionally pulmonary oedema can be rapidly fatal and require immediate intervention by emergency tracheotomy, thoracocentesis and evacuation of pleural air or administration of furosemide and oxygen, if available. Acute severe asthma and substantial pleural effusion are often not an immediate threat to life but nonetheless require fast intervention including administration of bronchodilators and corticosteroids or pleurocentesis, respectively.

Effects of furosemide, acetazolamide and amiloride on renal cortical and medullary tissue oxygenation in non-anaesthetised healthy sheep.

It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the impact of clinically used diuretic drugs on the renal cortical and medullary microcirculation is unclear. Therefore, we examined the effects of three commonly used diuretics, at clinically relevant doses, on renal cortical and medullary perfusion and oxygenation in non-anaesthetised healthy sheep. Merino ewes received acetazolamide (250mg; n=9), furosemide (20mg; n=10) or amiloride (10mg; n=7) intravenously. Systemic and renal haemodynamics, renal cortical and medullary tissue perfusion and , and renal function were then monitored for up to 8h post-treatment. The peak diuretic response occurred 2h (99.4±14.8mL/h) after acetazolamide, at which stage cortical and medullary tissue perfusion and were not significantly different from their baseline levels. The peak diuretic response to furosemide occurred at 1h (196.5±12.3mL/h) post-treatment but there were no significant changes in cortical and medullary tissue oxygenation during this period. However, cortical tissue fell from 40.1±3.8mmHg at baseline to 17.2±4.4mmHg at 3h and to 20.5±5.3mmHg at 6h after furosemide administration. Amiloride did not produce a diuretic response and was not associated with significant changes in cortical or medullary tissue oxygenation. In conclusion, clinically relevant doses of diuretic agents did not improve regional renal tissue oxygenation in healthy animals during the 8h experimentation period. On the contrary, rebound renal cortical hypoxia may develop after dissipation of furosemide-induced diuresis.

Death Due to Furosemide Anaphylaxis and The Importance of Serum Tryptase Level in Diagnosing Anaphylaxis: A Case Report

Anaphylaxis is a severe systemic hypersensitivity reaction with a sudden onset and may result in death. In this study, we report the case of a 71-year-old female patient who died within seconds after the administration of intravenous furosemide in emergency service; she had high serum tryptase levels at postmortem examination and nonspecific findings at autopsy, and death due to anaphylaxis was reported. With this study, we wanted to point to the rare and potentially fatal drug anaphylaxis, such as furosemide anaphylaxis. Also, our results indicate the importance of serum tryptase levels in the diagnosis of death due to anaphylaxis.

Evaluation of renal tubular function by multiparametric functional MRI in early diabetes

PurposeTo evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI.MethodsTwenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests.ResultsAt baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide – pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively).Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

Spleen white pulp structural and cellular composition in experimental furosemide-­induced hypomagnesemia

Relevance. Magnesium deficiency in the blood (hypomagnesemia) is due to many reasons, among which loop diuretics (furosemide) occupy acertain place. The role of the spleen in this process has not been determined. The aim of the work was to elucidate the effect of furosemide-­induced hypomagnesemia on the immune structures of the white pulp of rat spleen. Materials and Methods. Furosemide (Lasix® Aventis Pharma Ltd, India) was injected daily intraperitoneally at adose of 30 mg/kg to the experimental group of white outbred rats for 6 days, animals of the control group received an injection of 0.9% NaCl. Investigated: blood serum for the content of magnesium, calcium, sodium and iron; serial sections of the white pulp of the spleen after staining with hematoxylin and eosin to assess the structure and azure-­II-eosin to assess the cellular composition. With amicroscope magnification of 280 times, the ratio (in%) of primary (PLNS) and secondary lymphoid nodules of the spleen (SLNS) was calculated, the following were measured (µm): the diameter of the germinal center (GC), the width of the mantle and marginal zone, the diameter of the periarteriolar lymphoid sheath (PALS). In GC, the peripheral zone of lymphoid nodules, PALS at amagnification of 1500 times per field of view (100 μm2) was counted and presented as apercentage of the number of lymphocytes; macrophages; cells, mitotic and apoptotic elements. Morphometric analysis was carried out using Image ProPlus6.0 software (Media Cybernetics, USA). Statistical processing was carried out using the Statistica 10.0 software package with the determination of the arithmetic mean (M) and its error (m). Results and Discussion. The administration of furosemide led to adecrease in magnesium in the blood serum by 1.6 times (p0.05). In the white pulp of the spleen of animals of the experimental group, the proportion of SLNS decreased by 18.14%, the number of SLNS increased by 42.5% (p0.05). The diameter of SLNS increased insignificantly, the diameter of GC and the width of the marginal zone significantly increased by 27.1 and 24.8%, respectively. The proportion of macrophages increased by 20.6% in GC SLNS, and by 17.0% in PALS. The highest increase in the proportion of cells with signs of apoptosis was found in the periarteriolar lymphoid sheath of experimental animals - 34.6% (p0.05). Conclusion. Furosemide loading causes the development of dyselementosis, with the most significant loss of magnesium (hypomagnesemia) and has apronounced effect on the immune parameters of the spleen, represented by white pulp structures. Therefore, correction of the elemental status and monitoring of the state of the spleen in hypomagnesemia caused by the use of loop diuretics is anecessary element in the prevention of complications associated with the use of diuretic drugs.