Management of chronic hypertension during pregnancy with furosemide,amlodipine or aspirin: a pilot clinical trial

Abstract

Objective: To determine the maternal and neonatal efficacy and safety with furosemide, amlodipine or aspirin in women with mild/moderate chronic hypertension during pregnancy.

Methods: A pilot clinical trial was performed in a tertiary teaching hospital in Panama. Pregnant patients with mild/moderate chronic hypertension at ≤20 weeks of gestation were invited to take part in the study. Mild/moderate chronic hypertension was defined as a pregnancy with systolic blood pressure of 140–159?mmHg or diastolic blood pressure of 90–109?mmHg. Women in the furosemide group received 20?mg of furosemide oral each day, those in the amlodipine group received 5?mg of amlodipine oral each day and those in the aspirin group received 75?mg of orally-administered acetylsalicylic acid each day.

Results: We enrolled 63 patients during the study period, 21 women were randomised to each group (aspirin, amlodipine and furosemide). We found no difference in maternal complications, pre-term births, mean birth weight or in the proportion of small for gestational age infants among treatment groups. Severe hypertension and aggregate pre-eclampsia were similar among treatment groups.

Conclusion: This pilot trial demonstrates that both furosemide and amlodipine might have the same effect during pregnancy. However, a large clinical trial is necessary to prove this.     

呋噻米对急进高原大鼠血气影响

目的探讨急进4300m海拔条件下呋噻米对大鼠血气的影响。方法实验Wistar雄性大鼠40只,分为A组（平原对照组）、B组（高原对照组）、C组（高原呋噻米组）及D组（高原乙酰唑胺组）4组。在各处标准饲养3d后腹主动脉取血测定血气。结果各组血气结果有不同程度的改变。C组与B组相比,Po2、HCT、K^＋、ctHb、CB及ctO2均下降（P〈0．05）;SatO2百分比显著升高（P〈0．05）,机体有一定程度的呼吸性碱中毒或代谢性酸中毒。结论在4300m海拔低氧低气压条件下机体的血气发生一定程度的改变,应用呋噻米能一定程度改善大鼠缺氧状态。     

肝腹水患者合用呋塞米与甘露醇致急性肾损伤风险因素分析及预测

目的：分析肝腹水患者联合使用呋塞米与甘露醇发生急性肾损伤（acute kidney injury,AKI）的风险因素并建立风险预测模型。方法：回顾性分析2017年1月至2019年12月期间在新疆医科大学第一附属医院联合使用呋塞米和甘露醇的115例肝腹水住院患者资料,对可能发生AKI不良反应的危险因素进行单因素分析及Logistics回归分析,并在此基础上建立发生AKI的风险预测模型。结果：发生AKI的患者34例（29.57%）,Logistics回归分析结果显示,中性粒细胞百分比和胆汁酸2个影响因素对发生AKI有显著性影响（P<0.05）。进一步得到发生AKI的联合预测因子Y,其受试者工作特征（receiver operator characteristic,ROC）曲线的曲线下面积（area under curve,AUC）为0.709,表明有较好的预测能力。结论：中性粒细胞百分比和胆汁酸是肝腹水患者联合使用呋塞米与甘露醇发生AKI的独立危险因素,在临床治疗过程中,可将上述因素代入联合预测因子的计算公式,应注重AKI风险的评估,以保证临床用药的合理性。     

联合干预离子通道提高PVDF膜富集胎儿有核红细胞的效率

目的通过干预细胞膜阴离子通道(AE)和Na+/K+/2Cl-离子共转运体(NKCC),提高聚偏二氟乙烯(PVDF)膜富集脐血有核红细胞(NRBC)的效率。方法以密度为1.067的分离液分离NRBC,用AE抑制剂维拉帕米(verapamil)和NKCC抑制剂呋噻米(furosemide)联合干预,用流式细胞技术和巢式PCR观察干预前后离心法和过5μm孔径PVDF膜法富集NRBC的效率。结果最佳离心分离密度梯度为1.067。流式细胞仪检测离心分离的NRBC平均纯度为2.54%,干预后离心分离NRBC纯度为9.36%,NRBC富集率提升近3.7倍;过PVDF膜前NRBC为0.83%,过膜后NRBC为6.15%,干预后过膜将NRBC富集率提升了7.4倍。用巢式PCR检测,每ml血样中NRBC为120个时,干预后过膜的扩增条带的密度值由4.48升高至17.78,提升近4倍。结论维拉帕米和呋噻米能够通过改变脐血细胞性状,提高NRBC通过PVDF膜的效率。     

Chronic Reduction of Endocochlear Potential Reduces Auditory Nerve Activity: Further Confirmation of an Animal Model of Metabolic Presbyacusis

Gerbils aged in quiet show a decline of the endocochlear potential (EP) and elevated auditory nerve compound action potential (CAP) thresholds. However, establishing a direct relationship between an age-related reduction in the EP and changes in the activities of primary auditory neurons is difficult owing to the complexity of age-related histological changes in the cochlea. To address this issue, we developed a young gerbil model of “metabolic” presbyacusis that uses an osmotic pump to deliver furosemide into the round window niche for 7 days, resulting in a chronically reduced EP. In this model, the only major histopathologic changes were restricted to the hook region of the cochlea and consisted of loss of strial intermediate cells and massive edema in the lateral wall. The morphological and physiological evidence suggests that the cochlea can adapt to furosemide application over time. The morphology of spiral ganglion cells and hair cells appeared normal throughout the cochlea. CAP responses and EP values in this model are similar to those of quiet-aged ears. The spontaneous activity of single auditory fibers (n = 188) was assessed in 15 young gerbils treated with furosemide for 7 days. The percentage of recorded low-spontaneous rate (SR) fibers at characteristic frequencies (CFs) ≥ 6 kHz was significantly lower in furosemide-treated than in control ears. Recovery function tests of CAP responses after prior stimulation also showed a decline in activity of the low-SR population with CFs ≥ 6 kHz in the treated cochleas. A similar loss in the activity of low-SR fiber has been previously shown in quiet-aged gerbils. These results suggest that dysfunction of the cochlear lateral wall and subsequent chronic reduction in the EP can directly affect the activity patterns of primary auditory neurons in a manner similar to that seen in aged gerbils.     

Medullary nephrocalcinosis associated with long-term furosemide abuse in adults.

BACKGROUND: The use of furosemide is well recognized as a predisposing factor of nephrocalcinosis in infants. Although furosemide is widely used for various medical conditions in adults, its association with nephrocalcinosis in adults is not well established. METHODS: We studied 18 consecutive adult patients (male:female ratio 1:17, age range 21-59 years) who habitually took furosemide to control weight or oedema for long periods of time (range 3-25 years). The daily dose of continuous intake of furosemide ranged from 40 to 2800 mg. Nephrocalcinosis was evaluated using renal ultrasonography (US), computed tomography (CT), or kidney biopsies. RESULTS: Renal US and CT revealed bilateral nephrocalcinosis of the medullary pyramids in 15 (83.3%) out of 18 patients. The duration of furosemide abuse was similar between nephrocalcinosis positive (NC(+)) and nephrocalcinosis negative (NC(-)) groups. The daily dose of furosemide was nearly 10 times higher in the NC(+) group (range 120-2800 mg, mean 538 mg) than the NC(-) group (range 40-80 mg, mean 67 mg). All patients showed variable degrees of renal insufficiency and there was no difference in creatinine clearance between the NC(+) and NC(-) groups (P>0.05). Kidney biopsies performed in three patients showed focal tubulo-interstitial fibrosis and atrophy and calcifications were observed in outer medullary tubulo-interstitium. CONCLUSIONS: Long-term furosemide abuse can cause medullary nephrocalcinosis in adults, and the risk of developing of nephrocalcinosis seems to be correlated with the daily dose of furosemide. We suggest that long-term furosemide abuse should be suspected in adult patients when medullary nephrocalcinosis is incidentally detected by US or CT.     

Encephalopathy after furosemide use in nephrotic syndrome

An 18-year-old girl with nephrotic syndrome presented with a life-threatening respiratory failure and a severe encephalopathy, shortly after being started on furosemide. The evaluation confirmed furosemide as the sole culprit for the clinical manifestations. This case highlights an unpredictable dose-response relationship of furosemide. The pathophysiological basis, differential diagnosis and clinical implications of the observed findings are discussed.     

Negative modulation of nitric oxide production by neurotensin as a putative mechanism of the diuretic action of SR 48692 in rats

1. We investigated the effect of the non-peptide neurotensin (NT) antagonist SR 48692 on renal function in rats and the involvement of nitric oxide (NO) in the diuretic action of this compound.
2. In fed animals, SR 48692 dose-dependently (0.5 to 12.5 mg kg⁻¹, p.o., 0.03 to 1 mg kg⁻¹, i.p. and 0.1 to 1 μg/rat, i.c.v.) increased urine output and urinary excretion of Na⁺, K⁺ and Cl⁻ and reduced urine osmolality. The diuretic activity was also evident in water-deprived, fasted animals and in fasted, water-loaded rats.
3. NT (0.1 μg/rat, i.c.v.) had no effect on urine output in fed rats, but reduced the diuretic action of SR 48692 (1 μg/rat, i.c.v.). The opposite result was obtained in fasted, water-loaded animals: NT dose-dependently (0.01 and 0.1 μg/rat, i.c.v.) inhibited diuresis and this effect was significantly inhibited by i.c.v. SR 48692. In this experimental condition, SR 48692 did not further increase the on-going diuresis.
4. The NO synthesis inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME; 30 mg kg⁻¹, i.p.) alone had no effect on urine output in fed rats but prevented the diuretic action of i.c.v. or i.p. SR 48692; L-arginine (1 g kg⁻¹, i.p.) but not D-arginine (1 g kg⁻¹, i.p.) restored the SR 48692-dependent increase in diuresis. L-NAME had no effect on furosemide-stimulated diuresis.
5. Systemically administered L-NAME or i.c.v. NT in fasted, water-loaded rats significantly reduced water diuresis but this effect was no longer seen in animals given i.p. L-arginine. Rats receiving i.c.v. NT, whose diuresis was significantly reduced, also excreted less nitrates and nitrites in urine.
6. Increased diuresis after central or systemic administration of SR 48692 to fed rats was paralleled by increased urinary excretion of nitrates and nitrites, this being consistent with peripheral enhancement of NO production after NT-receptor blockade by SR 48692. The increase in diuresis after furosemide also involved an increase of nitrates and nitrites in urine, but this effect was about half that attained with an equipotent diuretic dose of SR 48692.
7. In fed rats, the NO donor isosorbide-dinitrate, reduced systolic blood pressure (unlike SR 48692 which did not affect blood pressure) but also dose-dependently (1 and 5 mg kg⁻¹, i.p.) stimulated urine output.
8. The overall effects of SR 48692 strongly support a link between the actions of endogenous NT, AVP and peripheral NO production in the modulation of renal excretion of water, Na⁺, K⁺ and Cl⁻.

     

Reversal of bronchial obstruction in children with mild stable asthma by aerosolized furosemide

Aerosolized furosemide has been shown to prevent the worsening of different variables in pulmonary function testing, following exercise or bronchial provocation with numerous agents. To investigate if aerosolized furosemide has a bronchodilator effect, we performed two prospective, randomized, placebo-controlled, double-blinded and crossover studies of four aerosol regimens in children with mild chronic asthma. In a pilot study examining three different doses of furosemide in 11 children, the dose of 1.0 mg/kg resulted in a mean maximum increase of 30.0 ± 6.8% in forced expiratory flow between 25 and 75% vital capacity (FEF_25–75), compared with a 3.1 ± 6.8% increase after aerosolized normal saline. The effect was observed after 10 minutes with a mean percent change of 17.7 ± 1.7% from baseline, that persisted to 30 minutes (19.3 ± 3.7%) and was significantly greater than that seen following aerosolized placebo (1.4 ± 2.9% and 0.7 ± 3.4%. respectively; P < 0.05). We then compared the effect of furosemide with that of aerosolized albuterol (0.15 mg/kg) in 18 patients. There was no statistically significant difference in the improvement observed in forced expiratory volume in 1 second (FEV₁) for albuterol (15.0 ± 2.7%) compared with furosemide (12.1 ± 2.9%) or in FEF_25–75 (42.9 ± 9.0% versus 26.3 ± 6.7%). The addition of albuterol to furosemide resulted in a 17.2 f 5.9% increase in FEV, and a 51.1 2 13.9% increase in FEF_25–75. Our results indicate that aerosolized furosemide has a bronchodilator effect in children with mild stable asthma. Pediatr Pulmonal. 1994;18:93–98. © 1994 Wiley-Liss, Inc.