Furosemide Administration Research Articles

MTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening.

The mammalian target of rapamycin (mTOR) signaling plays a critical role in cell homeostasis, growth and survival. Here, we investigated the localization of the main mTOR signaling proteins in the organ of Corti of normal-hearing and deafened guinea pigs, as well as their possible modulation by exogenously administered brain-derived neurotrophic factor (BDNF) in deafened guinea pigs. Animals were ototoxically deafened by systemic administration of kanamycin and furosemide, and one week later, the right cochleas were treated with gelatin sponge soaked in rhBDNF, while the left cochleas were used as negative controls. Twenty-four hours after treatment, animals were euthanized, and the cochleas were processed for subsequent analysis. Through immunofluorescence, we demonstrated the localization of AKT, pAKT, mTOR, pmTOR and PTEN proteins throughout the cochlea of guinea pigs for the first time, with a higher expression in supporting cells. Moreover, an increase in mTOR immunostaining was observed in BDNF-treated cochleas by means of fluorescence intensity compared to the other groups. Conversely, Western blot analysis showed no significant differences in the protein levels between groups, probably due to dilution of proteins in the neighboring tissues of the organ of Corti. Altogether, our data indicate that mTOR signaling proteins are expressed by the organ of Corti (with a major role for supporting cells) and that the modulation of mTOR may be a protective mechanism triggered by BDNF in the degenerating organ of Corti.

Furosemide does not reduce the incidence of postoperative acute kidney injury in adult patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis.

Acute kidney injury (AKI) is a common complication of cardiac surgical patients, the occurrence of which is multifactorial. Furosemide is the most common loop diuretic and widely used in cardiac surgery to reduce fluid overload, increase tubular flow and urine output. It remains unknown whether furosemide affects the incidence or prognosis of cardiac surgery-induced acute kidney injury (CS-AKI). Therefore, the current study was performed to address this question. PubMed, Embase, Scopus, Cochrane Library, and Web of Science databases were searched for relevant studies. Primary outcomes of interest included postoperative CS-AKI incidence, need for renal replacement therapy (RRT) rate. Secondary outcomes of interest included postoperative serum creatinine (Scr) and blood urea nitrogen (BUN) levels, postoperative mechanical ventilation duration (MVD), length of stay (LOS) in intensive care unit (ICU) and in hospital, and mortality. The odds ratio (OR) and/or the weighted mean difference (WMD) with 95% confidence interval (CI) were used to pool the data. Database search yielded six studies including 566 adult patients, and 283 patients were allocated into Group Furosemide and 283 into Group Control (Placebo). Heterogeneity between studies was deemed acceptable, and the publication bias was low. Meta-analysis suggested that furosemide administration in adult cardiac surgical patients had no effect on CS-AKI incidence (n = 4 trials; OR = 0.92; 95% CI: 0.37-2.30; p = .86; I2 = 57%) and need for RRT rate (n = 2 trials; OR = 4.13; 95% CI: 0.44-38.51; p = .21; I2 = 0%). Diversely, furosemide administration in adult cardiac surgical patients significantly decreased postoperative BUN level (n = 3 trials; WMD = 0.71; 95% CI: 0.10-1.33; p = .02; I2 = 0%), postoperative MVD (n = 2 trials; WMD = -3.13; 95% CI: -3.78 to -2.49; p < .00001; I2 = 0%) and postoperative LOS in ICU (n = 3 trials; WMD = -0.47; 95% CI:-0.76 to -0.18; p = .001; I2 = 0%). However, it had no significant impact on postoperative Scr level, postoperative LOS in hospital, and postoperative mortality. This meta-analysis suggested that furosemide administration in adult cardiac surgical patients had no significant effect on CS-AKI incidence, need for RRT rate, postoperative Scr level, LOS in hospital and mortality, but could reduce postoperative BUN level, MVD, and LOS in ICU. As only a limited number of studies were included, these results should be interpreted carefully and cautiously. Future high-quality randomized controlled trials are needed to define the role of furosemide in CS-AKI prevention and management.

Ureteroscopic Lithotripsy in Reverse Trendelenburg Position and Intraoperative Furosemide.

Upward stone migration is a significant problem during ureteroscopic lithotripsy (URSL) for upper ureteral stone, especially in absence of a ureteral occlusion device. In this study, we evaluated the novel strategy of reverse Trendelenburg position (RTP) and intraoperative diuresis for URSL without ureteral occlusion devices to avoid upward migration. From March 2018 to May 2020, a total of 119 URSLs were performed for upper ureteral stone (6-15 mm) with 67 procedures in RTP and 52 procedures in conventional lithotomy position (CLP). 20 mg of intravenous furosemide was administered prior to stone fragmentation with holmium laser only in RTP group. Patient demographics, stone side, stone size and operative characteristics were recorded and compared between the two groups. Patient data, stone side and size were similar in the two groups. All procedures were complete without conversion to open surgery and major complications. There was no significant difference in the mean operative time (47.9 ± 7.7 min vs 45.3 ± 7.0 min, P = .062) and mean hospital stay (3.9 ± 0.9 d vs 4.0 ± 1.0 d, P = .336) between the RTP and CLP group. Stone upward migration was significantly less in RTP group (3.0%, 2/67) than in CLP group (19.2%, 10/52) (P = .005). Stone-free rate at one month after initial treatment was 92.5% in RTP group and 73.1% in CLP group (P = .004). The strategy of placing the patient in RTP and intraoperative administration of intravenous furosemide is simple, feasible and cost-effective in preventing stone upward migration during URSL with holmium laser in absence of a ureteral occlusion device for upper ureteral stone.

Дорожная карта перкутанного доступа в почку под ультразвуковым контролем

The key point of successful PCNL is getting access to the renal collecting system. Ureteral catheterization and injection of contrast material provide an important advantage of visualizing and dilating the collecting system. However, catheterization increases the operation time, exposure to anesthesia, and requires additional reusable and disposable medical supplies. The purpose of the study was to develop a surgical algorithm for accessing the renal collecting system for mini-PCNL without catheterization.We analyzed the treatment results of 82 patients with a single kidney stone, who underwent mini-PCNL without prior catheterization of the ureter. The percutaneous access was obtained according to the roadmap we had developed. The puncture was performed under X-ray control and US guidance. For a calyx stone, the puncture was performed "to the stone". For a pelvis stone, the targeted calyx was accessed using the following algorithm where each next step was performed if the puncture had been impossible at the previous one: 1. 30 min before the operation: infusion load of normal saline, 1000 ml. 2. Intraoperatively: intravenous furosemide, 60 mg. 3. Puncture "to the pelvic stone", injecting contrast material into the collecting system and correcting the access puncture through the required calyx.In all 82 cases, puncture access was performed without ureteral catheterization. In 20 patients with calyceal stones, puncture onto a stone was successfully performed in 100% of the cases. Of 62 patients with pelvic stones, preliminary infusion was enough to allow a successful puncture in 49 (79%), access after intravenous administration of furosemide was obtained in 13 (21%), and a primary puncture onto a pelvic stone had to be done in 6 (10%) patients.Our proposed algorithm for accessing the PCS of the kidney was successfully used in 100% of the cases. It makes possible to avoid routine ureteral catheterization and thus reduce the overall operation time and the risk of complications, as well as save medical supplies. Clearly, such results require that the surgeon should have significant experience with puncture interventions under ultrasound control.

Intratympanic Administration of Dieckol Prevents Ototoxic Hearing Loss.

Objective. Systemic administration of dieckol reportedly ameliorates acute hearing loss. In this study, dieckol was delivered to the inner ear by the intratympanic route. The functional and anatomic effects and safety of dieckol were assessed using the rat ototoxicity model. Materials and methods. Dieckol in a high-molecular-weight hyaluronic acid vehicle (dieckol+vehicle group) or vehicle without dieckol (vehicle-only group) were randomly delivered into 12 ears intratympanically. Ototoxic hearing loss was induced by intravenous administration of cisplatin, gentamicin, and furosemide. The hearing threshold and surviving outer hair cells (OHC) were enumerated. Biocompatibility was assessed by serial endoscopy of the tympanic membrane (TM), and the histology of the TM and the base of bulla (BB) mucosa was quantitatively assessed. Results. The hearing threshold was significantly better (difference of 20 dB SPL) in the dieckol+vehicle group than in the vehicle-only group. The number of surviving OHCs was significantly greater in the dieckol+vehicle group than in the vehicle-only group. There were no signs of inflammation or infection in the ear. The thickness of the TM and the BB mucosa did not differ between the two groups. Conclusion. Intratympanic local delivery of dieckol may be a safe and effective method to prevent ototoxic hearing loss.

71-Year-Old Man With a New Heart Murmur

71-Year-Old Man With a New Heart Murmur

Comparison of Different Furosemide Regimens in the Treatment of Acute Heart Failure: A Meta-Analysis.

Background To compare the effects of different dosing schemes of furosemide on acute heart failure (AHF). Methods Literature that compared the efficacy of continuous and intermittent administration of furosemide in AHF patients was retrieved from PubMed, Embase, the Cochrane Library, and ISI Web of Science from inception to May 2022. The primary endpoints included overall weight loss, 24-hour urine volume, length of hospital stay, 24-hour brain natriuretic peptide (BNP) level change, and all-cause mortality. The RevmMan5.4 software was used to analyze the extracted data. Results A total of 10 studies with 775 patients, including 338 receiving continuous furosemide administration and 387 receiving intermittent furosemide administration, were included. The analysis results showed significant differences in weight loss (MD = 1.08, 95% CI (0.75~1.40), P < 0.00001) and 24-hour urine volume (MD =335.23, 95% CI (140.98~529.47), P = 0.0007) between the 2 groups. There was no significant difference in terms of length of hospital stay (MD = −0.71, 95% CI (-2.74~1.31), P = 0.49) and all-cause mortality (RR = 1.59, 95% CI (0.92~2.75), P = 0.10). Conclusions Compared with intermittent administration, continuous infusion of furosemide had a significant effect on the 24-hour urine volume and total weight loss in patients with AHF.

A novel contrast-induced acute kidney injury mouse model based on low-osmolar contrast medium

The contrast-induced acute kidney injury (CI-AKI) has been becoming the third common cause of hospital-acquired acute kidney injury. An ideal animal model is essential for understanding the pathophysiology of CI-AKI. Previous CI-AKI studies were mostly performed on rats with high-osmolar contrast medium (HOCM), which is unsuitable for transgenic researches. This study provides a novel, efficient and reproducible CI-AKI model which was developed in mouse by administrating a low-osmolar contrast medium (LOCM). First of all, we applied the frequently used pretreatments (uninephrectomy and water deprivation), which combined with HOCM on rats could induce CI-AKI, on mice with LOCM. Secondly, we attempted to find a novel pretreatment suitable for mouse and LOCM by combining two classic pretreatments(uninephrectomy, water deprivation and furosemide administration). Finally, we evaluate the kidney damage of the novel model. We found that this mouse model possessed a significant reduction in renal function, severe renal tissue damage, and increased renal tubular cells apoptosis, indicating that LOCM is a feasible inducer for CI-AKI mice model. Taken together, we found that uninephrectomy (UPHT) combined with 24 h water deprivation and furosemide administration 20 min before LOCM (iohexol, 10 ml/kg) application is a feasible pretreatment to establish a novel CI-AKI mouse model.

Rhabdomyolysis-Induced AKI (RIAKI) Including the Role of COVID-19

Rhabdomyolysis is a compound disease that may be induced by many factors, both congenital and acquired. Statin therapy is considered one of the most common acquired factors. However, recent scientific reports suggest that serious complications such as rhabdomyolysis are rarely observed. Researchers suggest that, in many cases, side effects that occur with statin therapy, including muscle pain, can be avoided with lower-dose statin therapy or in combination therapy with other drugs. One of the most recent agents discovered to contribute to rhabdomyolysis is COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rhabdomyolysis is defined as a damage to striated muscle cells with escape of intracellular substances into the bloodstream. These substances, including myoglobin, creatine kinase (CK), potassium, and uridine acid, are markers of muscle damage and early complications of rhabdomyolysis. Symptoms may be helpful in establishing the diagnosis. However, in almost 50% of patients, they do not occur. Therefore, the diagnosis is confirmed by serum CK levels five times higher than the upper limit of normal. One of the late complications of this condition is acute kidney injury (AKI), which is immediately life-threatening and has a high mortality rate among patients. Therefore, the prompt detection and treatment of rhabdomyolysis is important. Markers of muscle damage, such as CK, lactate dehydrogenase (LDH), myoglobin, troponins, and aspartate aminotransferase (AST), are important in diagnosis. Treatment of rhabdomyolysis is mainly based on early, aggressive fluid resuscitation. However, therapeutic interventions, such as urinary alkalinization with sodium bicarbonate or the administration of mannitol or furosemide, have not proven to be beneficial. In some patients who develop AKI in the course of rhabdomyolysis, renal replacement therapy (RRT) is required.

Association between focused cardiac ultrasound and time to furosemide administration in acute heart failure

BackgroundHeart failure (HF) is a global health burden, and its management in the emergency department (ED) is important. This study aimed to evaluate the association between focused cardiac ultrasound (FoCUS) and early administration of diuretics in patients with acute HF admitted to the ED. MethodsThis retrospective observational study was conducted at a tertiary academic hospital. Patients with acute HF patients who were admitted to the ED and receiving intravenous medication between January 2018 and December 2019 were enrolled. The main exposure was a FoCUS examination performed within 2 h of ED triage. The primary outcome was the time to furosemide administration. ResultsOf 1154 patients with acute HF, 787 were included in the study, with 116 of them having undergone FoCUS. The time to furosemide was significantly shorter in the FoCUS group (median time (q1–q3), 112 min; range, 65–163 min) compared to the non-FoCUS group (median time, 131 min; range, 71–229 min). In the multivariable logistic regression analysis adjusting for age, sex, chief complaint, mode of arrival, triage level, shock status, and desaturation at triage, early administration of furosemide within 2 h from triage was significantly higher in the FoCUS group (adjusted odds ratio, 1.63; 95% confidence intervals, 1.04–2.55) than in the non-FoCUS group. ConclusionsEarly administration of intravenous furosemide was associated with FoCUS examination in patients with acute HF admitted to the ED. An early screening protocol could be useful for improving levels in clinical practice at EDs.

Venous Leg Compression for Tissue Decongestion in Patients With Worsening Congestive Heart Failure.

AimsVenous leg compression (VLC) with elastic bandages has been proposed as a potentially useful strategy for decreasing tissue congestion. We aimed to evaluate the effect of VLC on short-term changes on intravascular refill, assessed by inferior vena cava (IVC) diameter in patients with worsening heart failure (WHF) requiring parenteral furosemide. Additionally, we sought to evaluate whether early changes in IVC were related to short-term decongestion.MethodsThis is a prospective study in which we included 20 consecutive ambulatory patients with WHF treated with subcutaneous furosemide and VLC for at least 72 h. The endpoints were (a) short-term changes in IVC, (b) the association between decongestion and 3-h IVC changes following VLC. Changes in continuous endpoints and their longitudinal trajectories were estimated with linear mixed regression models. All analyses were adjusted for multiple comparisons.ResultsFollowing administration of subcutaneous furosemide and VLC, we found a significant increase in 3-h IVC diameter (ΔIVC = 1.6 mm, CI 95%: 0.7–2.5; p < 0.001), with a greater increase in those with baseline IVC≤21 mm (2.4 vs. 0.8 mm; p < 0.001). 3-h intravascular refill (increase in IVC≥2 mm) was associated with greater decongestion (natriuresis, weight, peripheral edemas, and dyspnea) in those with baseline IVC≤21 mm but not when IVC>21 mm (p < 0.05 for all comparisons).ConclusionsIn this cohort of patients with congestive WHF treated with subcutaneous furosemide and VLC, we found a greater increase in short-term IVC in those with IVC ≤21 mm at baseline. In this subset of patients, a 3-h increase in IVC≥2 mm was associated with greater short-term decongestion.

Risk factors for acute kidney injury after major abdominal surgery in the elderly aged 75 years and above

ObjectivesThe study aimed to investigate the incidence and risk factors of acute kidney injury (AKI) in elderly patients (aged ≥ 75 years) undergoing major nonvascular abdominal surgery.MethodsThe study was a retrospective study that evaluated the incidence of AKI in patients within 48 h after major abdominal surgeries. Patients' preoperative characteristics and intraoperative management, including the use of nephrotoxic medications, were evaluated for associations with AKI using a logistic regression model.ResultsA total of 573 patients were included in our analysis. A total of 33 patients (5.76%) developed AKI, and 30 (90.91%), 2 (6.06%) and 1 (3.03%) reached the AKI stages 1, 2 and 3, respectively. Older age (adjusted OR, aOR 1.112, 95% confidence interval, CI 1.020–1.212), serum albumin (aOR 0.900, 95% CI 0.829–0.977), baseline eGFR (aOR 3.401, 95% CI 1.479–7.820), the intraoperative occurrence of hypotension (aOR 3.509, 95% CI 1.553–7.929), and the use of hydroxyethyl starch in combination with nonsteroidal anti-inflammatory drugs (aOR 3.596, 95% CI 1.559–8.292) or furosemide (aOR 5.724, 95% CI 1.476–22.199) were independent risk factors for postoperative AKI.ConclusionsSeveral risk factors, including intraoperative combined administration of HES and furosemide, are independent factors for AKI during abdominal surgeries. Anesthesiologists and surgeons should take precautions in treating at-risk patients.

Suspected postoperative phenylephrine‐associated pulmonary haemorrhage in a horse with nephrosplenic entrapment of the large colon

AbstractA 16‐year‐old, Irish sport horse was treated with intravenous fluid therapy and phenylephrine, followed by light exercise for a nephrosplenic entrapment of the left large colon. Medical treatment failed to return the colon to its normal position and an exploratory coeliotomy was performed. The surgical procedure and general anaesthesia were uneventfully completed; however, the horse developed haemoptysis, pulmonary oedema and epistaxis in the recovery box. The horse improved after administration of intravenous furosemide and hypertonic saline and was discharged from the hospital 4 days later. Phenylephrine is a sympathomimetic drug that causes splenic contraction and thereby decreases the size of the spleen, allowing the colon to return to its normal position. Fatal pulmonary and abdominal bleeding has been reported as a rare complication of phenylephrine treatment in horses. This case shows a delayed and completely unexpected presentation, which responded to supportive treatment.

Vaptans for oedematous and hyponatraemic disorders in childhood: A systematic literature review.

The aim of this study was to systematically review the use of vaptans (nonpeptide vasopressin receptor antagonists) in children. Through a database search (Web of Science, the National Library of Medicine, Excerpta Medica), we identified case series and case reports and extracted clinical and laboratory data. Twenty-six articles, published since 2008, reported on 226 patients. Among 115 children with hyponatraemic (n = 63) and oedematous disorders (n = 52), a 48 hour course of tolvaptan with an initial dose of 0.38 ± 0.27 mg/kg was administered in 106 cases, while intravenous conivaptan was reported in nine cases. An increase (P < .02) in urine output was shown in both oedematous (from 3.2 ± 2.0 to 5.3 ± 6.7mL/kg/day) and hyponatraemic (from 3.0 ± 1.5 to 4.4 ± 2.3mL/kg/day) patients. In these latter, sodium increased from 125 ± 6 to 133 ± 6mmol/L (P < .0001). The increase in sodium level correlated with its basal value, but not with the administered vaptan dose. Among 111 children undergoing cardiac surgery, after tolvaptan 0.21 ± 0.01 mg/kg/day, mostly combined with conventional diuretics, an increase in diuresis by 41 ± 4% was seen within 24 hours (P < .0001). Similarly, a single add-on dose of tolvaptan 0.45 mg/kg allowed a reduced additional intravenous furosemide administration (0.26 ± 0.23 vs 0.62 ± 0.48 mg/kg, P < .005). Side effects were rarely reported, and included excessive thirst and xerostomia in seven, skin rash in one and elevated aminotransferases in one patient(s). Vaptans appear to be safe for oedematous and hyponatraemic disorders also in children. Although they increase diuresis and natraemia, no superiority to traditional diuretics and sodium supplements has been demonstrated. Reported side effects are rare and non-serious.

Loop‐Diuretics Increase Pendrin through alpha‐ketoglutarate receptor, Oxgr1

IntroductionIt is well appreciated that loop diuretic resistance is governed by pendrin and activation of the thiazide‐sensitive sodium chloride cotransporter, NCC. Recently, our lab discovered pendrin increases as the natriuretic response wanes, coincident with the activation of a‐ketoglutarate (AKG) synthesis, secretion of a‐KG into the pro‐urine, and increased gene expression of the AKG GPCR, Oxgr1. Here we test the hypothesis that activation of Oxgr1 is necessary for the development of loop diuretic resistance.Methods10 week old male OXGR1 KO and WT (C57B6J) mice were challenged with furosemide (100 mg/kg) for 4 days. Urine was collected over 24 hours, daily, and urinary electrolytes were measured. Mice were euthanized at the end of the experiment and plasma electrolytes and aldosterone levels were measured using standard methods. Cortical protein and RNA abundances were measured using western blot and qRT‐PCR, respectively.ResultsWT and OXGR1 KO displayed distinguishing phenotypes only after furosemide administration. The loop‐diuretic challenge increased pendrin protein in WT mice but not in the OXGR1 KO mice despite identical increases in the chief pendrin stimulators, aldosterone and metabolic alkalosis. Pendrin transcript increased to the same extent in both genotypes, indicating OXGR1 augments pendrin via a post‐translational mechanism. Even with compromised upregulation of pendrin, OXGR1 KO mice exhibited the same diuretic response as WT mice. Upregulation of NCC was not compromised in the OXGR1 mice.ConclusionOXGR1 is required for post‐translational upregulation of pendrin protein post diuretic challenge, consistent with activation of a aKG‐OXGR1‐pendrin signaling axis. Upregulation of NCC and residual pendrin activity may be sufficient to brake the loop‐diuretic response.

Utility of Real-Time Three-Dimensional Echocardiography for the Assessment of Right Ventricular Morphology and Function in Large Animal Models.

Real-time three-dimensional echocardiography (RT3DE) enables a noninvasive assessment of right ventricular (RV) morphology. However, no study has evaluated the relationship between RV function obtained by RT3DE and RV pressure-volume loops. This hypothesis-driven, experimental study aimed to assess the utility of RT3DE in the evaluation of RV morphology and function. Ten anesthetized beagle dogs sequentially underwent dobutamine infusion, acute infusion of lactated Ringer’s solution, and furosemide administration to alter RV contractility and loading conditions. RV pressure-volume loop-derived hemodynamic measurements and echocardiography, including two-dimensional speckle-tracking echocardiography and RT3DE, were performed in each study protocol. Bland–Altman analysis showed strong agreement in RV volume, ejection fraction, and stroke volume obtained by right heart catheterization and RT3DE. Multiple regression analyses revealed that the peak myocardial velocity of the lateral tricuspid annulus (RV s’) and global RV longitudinal strain rate were significantly associated with end-systolic elastance (adjusted r2 = 0.66, p < 0.001). RV s’, RV free wall longitudinal strain, and RT3DE-derived stroke volume/end-systolic RV volume ratio were associated with RV pressure-volume loops-derived end-systolic/arterial elastance ratio (adjusted r2 = 0.34, p < 0.001). RT3DE could detect the changes in catheterization-derived RV volume with a strong agreement and might be useful in estimating RV-pulmonary arterial coupling.

Comparison of static-fluid or excretory magnetic resonance urography with computed tomography urography for visualization of nondilated renal pelvises and ureters in healthy Beagles.

To assess the usefulness of magnetic resonance urography (MRU) for the visualization of nondilated renal pelvises and ureters in dogs and to compare our findings for MRU versus CT urography (CTU). 9 healthy Beagles. Dogs underwent CTU, static-fluid MRU, and excretory MRU, with ≥ 7 days between procedures. Contrast medium was administered IV during CTU and excretory MRU, whereas urine in the urinary tract was an intrinsic contrast medium for static-fluid MRU. For each procedure, furosemide (1 mg/kg, IV) was administered, and reconstructed dorsal plane images were acquired 3 minutes (n = 2) and 7 minutes (2) later. Images were scored for visualization of those structures and for image quality, diameters of renal pelvises and ureters were measured, and results were compared across imaging techniques. Excretory MRU and CTU allowed good visualization of the renal pelvises and ureters, whereas static-fluid MRU provided lower visualization of the ureters. Distention of the renal pelvises and ureters was good in excretory MRU and CTU. Distention of the ureters in static-fluid MRU was insufficient compared with that in CTU and excretory MRU. Distinct artifacts were not observed in CTU and excretory MRU images. Static-fluid MRU images had several mild motion artifacts. Our findings indicated that excretory MRU with furosemide administration was useful for visualizing nondilated renal pelvises and ureters of dogs in the present study. When performing MRU for the evaluation of dogs without urinary tract dilation, excretory MRU may be more suitable than static-fluid MRU.

Reversal of Trimethoprim-Induced Antikaliuresis in an HIV Patient With Pneumocystis Pneumonia

Abstract High-dose trimethoprim-sulfamethaxazole is the drug of choice for treatment of severe Pneumocystis jiroveci pneumonia (PJP) with the caveat that at higher doses, serious adverse events occur more frequently. A lethal complication is hyperkalemia which often mandates premature discontinuation of therapy despite lower efficacy of second-line agents. We report a case of a patient with severe PJP causing respiratory failure treated with high-dose trimethoprim-sulfamethaxazole who experienced hyperkalemia, which was successfully managed with a combination of fludrocortisone and furosemide allowing completion of antibiotic course. Administration of fludrocortisone and furosemide may enable practitioners to effectively address trimethoprim-induced hyperkalemia in critically ill patients with PJP. We speculate that exogenous administration of fludrocortisone may promote transcription of ENaC-amiloride sensitive epithelial sodium channels, which is unaffected by circulating trimethoprim allowing for kaliuresis to be restored. The addition of furosemide increases sodium load, further promoting potassium excretion.

Postoperative hyperthermia-induced multiple organ failure in a child with Down syndrome: a case report

BackgroundPsychological stress has been reported to cause hyperthermia. Persistent excessive hyperthermia can, in turn, cause hypercytokinemia and organ damage. We report a case of postoperative severe hyperthermia leading to a systemic inflammatory response and multiple organ failure in a child with Down syndrome.Case presentationA 10-month-old native Japanese boy with Down syndrome and Hirschsprung’s disease is described. Newborn screening showed congenital hypothyroidism and a ventricular septal defect, but these conditions were stable upon administration of levothyroxine and furosemide. His development was equivalent to that of a child with Down syndrome. He developed a noninfectious high fever twice after preoperative preparations at age 8 months and again at 9 months. He was readmitted to hospital at age 10 months to undergo the Soave procedure to correct Hirschsprung’s disease. However, he contracted a fever immediately after the surgical procedure. Hyperthermia (42 °C) was refractory to acetaminophen treatment and deteriorated to multiple organ failure due to hypercytokinemia, with increased serum levels of interleukin-6 (44.6 pg/mL) and interleukin-10 (1010 pg/mL). He died on postoperative day 2 with hypoxemia, respiratory/metabolic acidosis, increased serum levels of transaminases, reduced coagulation, and pancytopenia. Various infectious and noninfectious causes of hyperthermia could not be identified clearly by culture or blood tests.ConclusionsWe speculated that the proximate cause of the fever was psychological stress, because he suffered repeated episodes of hyperthermia after the invasive procedure. Hyperthermia, together with the immune-system disorders associated with Down syndrome, may have induced hypercytokinemia and multiple organ failure. This rare case of noninfectious postoperative hyperthermia leading to multiple organ failure may help to shed further light on the currently unclear pathogenic mechanism of hyperthermia and associated multiple organ failure during the perioperative period in children.

Evaluation of the stability of furosemide in tablet form during six-month storage in spaceflight and peculiarities of its pharmacokinetics and pharmacodynamics under conditions of anti-orthostatic hypokinesia.

The present study investigated the stability of furosemide under space-flight conditions on board the International Space Station, as well as its pharmacokinetics and pharmacodynamics under conditions simulating exposure to some space-flight factors. Quantitative analysis of furosemide tablets by HPLC was performed before spaceflight (background), then after six months storage under normal ground conditions (control) and under spaceflight conditions (SF). The pharmacokinetics and pharmacodynamics of furosemide were studied in six healthy volunteers after a single oral dose of 40mg under normal conditions (background) and under anti-orthostatic hypokinesia (ANOH). Quantitative content of furosemide in tablets before SF was 40.19±0.28mg (100.47±0.71%), after 6months storage: under normal conditions (control)- 39.9±0.39mg (99.73±0.98%), under SF- 39.24±0.72mg (98.11±1.80%), which was within the prescribed limits. Studying basic hemodynamic parameters showed that in ANOH conditions 6h after furosemide administration there was a statistically significant increase of the stroke volume (SV) (+36.5 Δ%), a tendency for increasing of the stroke index (SI) (+36.5 Δ%) and decreasing of the total peripheral resistance (TPR) (-21.9 Δ%) compared to baseline study. It has been established that various factors of space flight (overloading, excessive vibration, microgravity, etc.) do not negatively influence the stability of furosemide in tablet form during storage for 6months on board the International Space Station.