Hyponatremia in Liver Cirrhosis / 대한소화기학회지

Hyponatremia is a commonly observed complication that is related to hypoalbuminemia and portal hypertension in patients with advanced liver cirrhosis. Hyponatremia in patients with liver cirrhosis is mostly dilutional hyponatremia and is defined when the serum sodium concentration is below 130 meq/L. The risk of complications increases significantly in cirrhotic patients with hyponatremia, which includes spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. In addition, hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and is an important prognostic factor before and after liver transplantation. The conventional therapies of hyponatremia are albumin infusion, fluid restriction and loop diuretics, but these are frequently ineffective. This review investigates the pathophysiology and various therapeutic modalities, including selective vasopressin receptor antagonists, for the management of hyponatremia in patients with liver cirrhosis.

Hydrochlorothiazide does not increase furosemide's effects in end-stage renal disease

Diuretic therapy for the treatment of edema in patients with end-stage renal disease (ESRD) is unsatisfactory, and a combination of thiazide and loop diuretics may produce better clinical effects. To evaluate the influence of thiazide on loop diuretic therapy for ESRD, we performed a crossover study of furosemide versus hydrochlorothiazide plus furosemide treatment. The diuretic effects of furosemide (160 mg i.v.) alone versus a combination of hydrochlorothiazide (100 mg p.o.) and furosemide were studied in ten ESRD patients with proteinuria greater than 1 g/day. The diuretic effects were compared for 24 h urine volume and electrolyte excretion. To detect the influence of thiazide that may have been obscured in the widely dispersed data, pharmacodynamic analysis of urine furosemide excretion rate versus fractional excretion of sodium (FeNa) was also performed using mixed-effect modeling. Combination therapy was not significantly different from furosemide monotherapy in terms of 24 h urine volume, chloride, or sodium excretion. Hydrochlorothiazide was not a significant covariate in the furosemide effect for the pharmacodynamic model. In patients with ESRD and severe proteinuria (>1,000 mg/day), the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furosemide.

Loop Diuretics in Clinical Practice

Diuretics are commonly used to control edema across various clinical fields. Diuretics inhibit sodium reabsorption in specific renal tubules, resulting in increased urinary sodium and water excretion. Loop diuretics are the most potent diuretics. In this article, we review five important aspects of loop diuretics, in particular furosemide, which must be considered when prescribing this medicine: (1) oral versus intravenous treatment, (2) dosage, (3) continuous versus bolus infusion, (4) application in chronic kidney disease patients, and (5) side effects. The bioavailability of furosemide differs between oral and intravenous therapy. Additionally, the threshold and ceiling doses of furosemide differ according to the particular clinical condition of the patient, for example in patients with severe edema or chronic kidney disease. To maximize the efficiency of furosemide, a clear understanding of how the mode of delivery will impact bioavailability and the required dosage is necessary.

Medical Treatment of Acute Decompensated Heart Failure Syndrome / 대한내과학회지

Acute decompensated heart failure syndrome is the most common cause of cardiovascular hospitalization with a high rate of in-hospital mortality. The clinical presentation is characterized by different clinical profiles due to various underlying causes, precipitating factors, volume status, and tissue perfusion status. Therefore, clinicians should carefully examine the hemodynamic status of acute decompensated heart failure patients in the initial management. Risk stratification might provide guidance to clinicians who care for patients with acute decompensated heart failure syndromes, and might improve decision-making in emergent care when decisions must be made quickly and accurately. Intravenous loop diuretics are the main treatment option for the relief of congestive symptoms. This article reviews how to assess hemodynamic status of acute decompensated heart failure patients and how to perform risk stratification of patients. Additionally, the initial treatment approach with a variety of pharmacological therapies including inotropic agents, diuretics, beta-blockers, angiotensinogen converting enzyme-inhibitors, angiotensin receptor blockers, digoxin, and other medications that are routinely prescribed in the management of acute decompensated heart failure patients are also discussed.

Impact of loop diuretics on blood sodium in patients hospitalized for heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the level of blood sodium in patients hospitalized for heart failure with water-sodium retention treated with loop diuretics and risk factors of low blood sodium.</p><p><b>METHODS</b>We selected 1 378 acute decompensated heart failure patients who visited Anzhen Hospital, and they are treated with loop diuretics, 259 patients with weight loses more than 1 kg in one week was enrolled in the final analysis, and divided into 3 groups: Group A (weight reduction between 1-3 kg), Group B (weight reduction between 3-5 kg) and Group C (weight reduction over 5 kg). Blood sodium, creatinine and uric acid were compared among groups and risk factors of low blood sodium were analyzed.</p><p><b>RESULTS</b>Blood sodium was similar before and post loop diuretics treatment in Group A, and reduced in group B ((138.28 ± 3.73) mmol/L vs. (139.34 ± 3.66) mmol/L, P < 0.05) and in Group C((137.60 ± 4.07) mmol/L vs. (139.44 ± 4.12) mmol/L, P < 0.05). Forty-six (17.8%) patients developed hyponatremia post loop diuretics treatment. Duration of loop diuretics use was the independent risk infector for hyponatremia (OR = 1.191, 95%CI 1.010-1.385).</p><p><b>CONCLUSIONS</b>Loop diuretics use is safe for treating hospitalized patients for heart failure with water-sodium retention and the risk of developing hyponatremia is low. Duration of loop diuretics use is the independent risk factor of hyponatremia.</p>

model portraying experimental loss of hair cell: the use of distortion product otoacoustic emission in the assessment of rat's ear

The use of rats in research academies to study deafness is widespread, meanwhile medicinal methods to eliminate hair cells is also increasing. Thus, aminoglycosides and loop diuretics have grasped more attention. This study aimed at establishing an animal model in which a rapid distortion of the hair cell of cochlea administering amikacin and furosemide and using distortion product otoacoustic emission [DPOAE] the functioning of rat's ear would be assessed. Forty-eight male Sprague-Dawley rats [mean weight 200-250g] were randomly divided into six equal groups. Except the control group the rest received 0.5mg/g, 0.75mg/g, 1mg/g, 1.25mg/g, and 1.5mg/g, of subcutaneous amikacin respectively. 30 minutes later every rat received 0.1mg/g of furosemide intrapritoneally. DPOAE of rats was measured before these injections and 72 hours later. Then tissue sections of the rat's cochlea were prepared. All the cases had a significant decrease in their DPOAE with the frequencies 2KHz-8KHz [p

Renal Dysfunction in Acute Heart Failure

During treatment of acute heart failure (AHF), worsening renal function is often complicated and results in a complex clinical course. Furthermore, renal dysfunction is a strong independent predictor of long-term adverse outcomes in patients with AHF. Traditionally, the predominant cause of renal dysfunction has been attributed to impairment of cardiac output and relative underfilling of arterial perfusion. Recently, emerging data have led to the importance of venous congestion and elevated intra-abdominal pressure rather than confining it to impaired forward cardiac output as the primary driver of renal impairment. Relief of congestion is a major objective of AHF treatment but therapy is still based on the administration of loop diuretics. The results of the recently performed controlled studies for the assessment of new treatments to overcome resistance to diuretic treatment to protect kidneys from untoward effects have been mostly neutral. Better treatment of congestion in heart failure remains a major problem.

A Case of Cardiac Amyloidosis With Diuretic-Refractory Pleural Effusions Treated With Bevacizumab

Cardiac amyloidosis describes a clinical disorder caused by infiltration of abnormal insoluble fibrils in the heart, characterized by progressive heart failure and a grave prognosis. Pleural effusion in cardiac amyloidosis may represent a sign of heart failure, but it can also result from pleural infiltration of amyloid, manifested by recurrent large fluid accumulations. Recently, the role of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of refractory pleural effusion. We report a case of a 53 year-old female patient with cardiac amyloidosis who presented with recurrent accumulation of large pleural effusions. She was initially treated with high dose loop diuretics, but the pleural effusion persisted, with the daily amount of drainage averaging 1 L/day. Accumulation of pleural fluid did not subside after 3 cycles of melphalan/prednisolone therapy. After the introduction of bevacizumab, an anti-VEGF antibody, the amount of pleural effusion decreased significantly. Efficacy of anti-VEGF therapy for refractory pleural effusions needs to be defined through further studies.

Changes in sodium appetite evoked by lesions of the commissural nucleus of the tractus solitarius

Ablation of the area postrema/caudal nucleus of the tractus solitarius (NTS) complex increases sodium intake, but the effect of selective lesions of the caudal NTS is not known. We measured depletion-induced sodium intake in rats with electrolytic lesions of the commissural NTS that spared the area postrema. One day after the lesion, rats were depleted of sodium with furosemide (10 mg/kg body weight, sc) and then had access to water and a sodium-deficient diet for 24 h when 1.8 percent NaCl was offered. Water and saline intakes were measured for 2 h. Saline intake was higher in lesioned than in sham-lesioned rats (mean ± SEM: 20 ± 2 vs 11 ± 3 mL/2 h, P < 0.05, N = 6-7). Saline intake remained elevated in lesioned rats when the tests were repeated 6 and 14 days after the lesion, and water intake in these two tests was increased as well. Water intake seemed to be secondary to saline intake both in lesioned and in sham-lesioned rats. A second group of rats was offered 10 percent sucrose for 2 h/day before and 2, 7, and 15 days after lesion. Sucrose intake in lesioned rats was higher than in sham-lesioned rats only 7 days after lesioning. A possible explanation for the increased saline intake in rats with commissural NTS lesions could be a reduced gastrointestinal feedback inhibition. The commissural NTS is probably part of a pathway for inhibitory control of sodium intake that also involves the area postrema and the parabrachial nucleus.

Posterior circulation stroke in a young male following snake bite.

Neurological deficits can occur following snake bite. It is usually due to intracerebral haemorrhage or subarachnoid bleed as a result of depletion of clotting factors. A healthy 14-years-old male developed bilateral ptosis and altered sensorium within 3 hours of snake bite. CT Brain revealed bilateral cerebellar and right occipital infarction with mass effect. Clotting time and bleeding time were normal. The possible mechanism for infarction in this patient is discussed.

Mieux prescrire les diuretiques

Les diuretiques sont des medicaments couramment utilises en pratique clinique quotidienne. Bien que rarement utilises en automedication; une meilleure connaissance des risques et des benefices lies a ces medicaments peut permettre de mieux les utiliser en fonction de la situation clinique du patient

Chronic excitotoxic lesion of the dorsal raphe nucleus induces sodium appetite

We determined if the dorsal raphe nucleus (DRN) exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11) or 1 æg/0.2 æl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10) through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment) and a low dose of dietary captopril (1 mg/g chow). From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 ± 2.3 to 22.3 ± 4.6 ml 0.3 M NaCl intake) whereas PB-DRN did not exceed 2 ml (P < 0.001). Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 ± 3.8 vs 21.6 ± 3.9 ml 300 min after fluid offer, P < 0.001). Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 ± 4.3 and 32.5 ± 3.4 ml on day 1 and day 2, respectively, vs 20.2 ± 2.8 ml on day 0, P < 0.001). These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.

Proper Use of Diuretics

Diuretics are among the most commonly used drugs. They primarily block active reabsorption of sodium at different sites in the nephron, thereby increasing urinary losses of NaCl and H2O. This ability to induce a negative fluid balance has made these drugs particularly useful in the treatment of a variety of conditions, edematous: congestive heart failure, nephrotic syndrome, liver cirrhosis, chronic renal failure, idiopathic edema, and nonedematous states: hypertension, hypercalcemia, nephrolithiasis, and syndrome of inappropriate antidiuretic hormone secretion. The diuretics are generally divided into three major classes, which are distinguished by the sites at which they impair the sodium reabsorption: loop diuretics at the thick ascending limb of the loop of Henle, thiazide-type diuretics at the distal tubule, and potassium-sparing diuretics at the cortical collecting tubule. The loop diuretics that are generally the most potent are furosemide, torasemide, and ethacrynic acid. The thiazide-type diuretics include chlorothiazide and metolazone. Spironolactone and amiloride are potassium-sparing diuretics. Diuretics should be started at an effective single dose and given intermittently with a subsequent increase in dose or frequency of administration. As a general rule, the rate of diuresis in an edematous patient should not exceed 1 to 2kg weight loss per day. In renal failure patients, loop diuretics at a higher than normal dose are required to get the desired diuretic effect because the diuretic excretion is often limited, in part due to the retention of organic anions. The patients with liver cirrhosis are responsive to spironolactone. After the administration of diuretics, even if a net diuresis is induced, the response is short-lived as a new steady state is rapidly established because the diuretic-induced sodium losses are counterbalanced by neuro-humorally mediated increases in tubular reabsorption at nondiuretic sensitive sites. This process is called compensatory antidiuresis or diuretic tolerance. Therefore sodium restriction is important when a patient is taking loop diuretics, and the concurrent use of a thiazide diuretic can inhibit downstream NaCl reabsorption, resulting in an exaggeration of diuresis. The most common side-effects are those encountered in virtually all the effective drugs: hypovolemia, hypokalemia and potassium depletion, hyperuricemia, and metabolic alkalosis. Other side-effects include hyperglycemia, hyperlipidemia, hyperuricemia, ototoxicity and sexual dysfunction. In addition, diuretics have the potential to increase the toxicity of several other agents. Nonsteroidal antiinflammatory drugs may antagonize the natriuretic effects of diuretics. The combination of potassium-sparing diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers may result in severe hyperkalemia.

The Effect of Hyperventilation on Serum Potassium Concentration During Infusion of Mannitol / 대한마취과학회지

BACKGROUND: Mannitol is widely used in neurosurgical patients and may induce an increase in serum potassium concentration according to doses and administration rates with unknown mechanism. The treatment of hyperkalemia is aimed at eliminating the causes and includes calcium, sodium bicarbonate, glucose with insulin, loop diuretics and hyperventilation. This study was undertaken to observe the effects of hyperventilation on the serum potassium concentration following infusion of mannitol (2.0 gm/kg). METHODS: We studied 30 patients who were operated brain aneurysm clipping surgery and were divided into 3 groups (n=10). In control group, mild hypocapnia was maintained (PaCO2, 32 2 mmHg) before and after mannitol infusion. In group I, moderate hypocapnia was maintained (PaCO2, 27 2 mmHg) before and after mannitol infusion. In group II, mild hypocapnia (PaCO2, 32 2 mmHg) was maintained before 30 minutes of mannitol infusion and moderate hypocapnia (PaCO2, 27 2 mHg) after mannitol infusion. We started infusion of 20% mannitol with a dosage of 2.0 gm/kg, 15~20 min after cranium was opened. RESULTS: The changes of serum potassium were as follows (Mean SD mEq/l) (just before and 15min, 30min, 60min after mannitol infusion): 3.79 0.48, 4.66 0.60, 4.44 0.48, 4.13 0.40 (Control group), 3.62 0.18, 3.63 0.42, 4.14 0.51, 3.95 0.33 (Group I), 3.76 0.20, 3.91 0.15, 4.11 0.30, 4.04 0.23 (Group II). After 15 minutes of mannitol infusion, the serum potassium levels of group I and II were lower than that of control group (p<0.05) and there was no significant difference between group I and II. CONCLUSIONS: These results suggest that hyperventilation may blunt the increase in serum potassium concentration following rapid infusion of high dose mannitol.

Diagnosis and Management of Acute Renal Failure in Surgical Patient / 영남의대학술지

Acute renal failure refers to a rapid reduction in renal function that usually occurs in an individual with no known previous renal disease. Development of a complication of acue renal failure in critically ill surgical patients is not unusual, and it causes high morbidity and mortality. Acute renal failure can be divided as Pre-renal (functional), Renal (organic), and Postrenal (obstructive) azotemia according to their etiologies. Early recognition and proper correction of pre-renal conditions are utter most important to prevent an organic damage of kidney. These measures include correction of dehydration, treatment of sepsis, and institution of shock therapy. Prolonged exposure to ischemia or nephrotoxin may lead a kidney to permanent parenchymal damage. A differential diagnosis between functional and organic acute renal failure may not be simple in many clinical settings. Renal functional parameters, such as FENa+ or renal failure index, are may be of help in these situations for the differential diagnosis. Provocative test utilizing mannitol, loop diuretics and renovascular dilators after restoration of renal circulation will give further benefits for diagnosis or for prevention of functional failure from leading to organic renal failure. Converting enzyme blocker, dopamine, calcium channel blocker, and propranolol are also reported to have some degree of renal protection from bioenergetic renal insults. Once diagnosis of acute tubular necrosis has been made, all measures should be utilized to maintain the patient until renal tubular regeneration occurs. Careful regulation of fluid, electrolyte, and acid-base balance is primary goal. Hyperkalemia over 6.5 mEq/l is a medical emergency and it should be corrected immediately. Various dosing schedules for medicines excreting through kidney have been suggested but none was proved safe and accurate. Therefore blood level of specific medicines better be checked before each dose, especially digoxin and Aminoglycosides. Indication for application of ultrafiltration hemofilter or dialysis may be made by individual base.