Torsemide - Demadex Part Two

Torsemide - Demadex Part Two

Warnings

Hepatic Disease With Cirrhosis and Ascites

DEMADEX should be used with caution in patients with hepatic disease with cirrhosis and ascites, since sudden alterations of fluid and electrolyte balance may precipitate hepatic coma. In these patients, diuresis with DEMADEX (or any other diuretic) is best initiated in the hospital. To prevent hypokalemia andmetabolic alkalosis, an aldosterone antagonist or potassium-sparing drug should be used concomitantly with DEMADEX.

Ototoxicity

Tinnitus and hearing loss (usually reversible) have been observed after rapidintravenous injection of other loop diuretics and have also been observed after oral DEMADEX. It is not certain that these events were attributable to DEMADEX. Ototoxicity has also been seen in animal studies when very highplasma levels of torsemide were induced. Administered intravenously, DEMADEX should be injected slowly over 2 minutes, and single doses should not exceed 200 mg.

Volume and Electrolyte Depletion

Patients receiving diuretics should be observed for clinical evidence of electrolyte imbalance, hypovolemia, or prerenal azotemia. Symptoms of these disturbances may include one or more of the following: dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps,muscular fatigue, hypotension, oliguria, tachycardia, nausea, and vomiting. Excessive diuresis may cause dehydration, blood-volume reduction, and possibly thrombosis and embolism, especially in elderly patients. In patients who develop fluid and electrolyte imbalances, hypovolemia, or prerenal azotemia, the observed laboratory changes may include hyper- or hyponatremia, hyper- orhypochloremia, hyper- or hypokalemia, acid-base abnormalities, and increasedblood urea nitrogen (BUN). If any of these occur, DEMADEX should be discontinued until the situation is corrected; DEMADEX may be restarted at a lower dose.

In controlled studies in the United States, DEMADEX was administered tohypertensive patients at doses of 5 mg or 10 mg daily. After 6 weeks at these doses, the mean decrease in serum potassium was approximately 0.1 mEq/L. The percentage of patients who had a serum potassium level below 3.5 mEq/L at any time during the studies was essentially the same in patients who received DEMADEX (1.5%) as in those who received placebo (3%). In patients followed for 1 year, there was no further change in mean serum potassium levels. In patients with congestive heart failure, hepatic cirrhosis, or renal disease treated with DEMADEX at doses higher than those studied in United Statesantihypertensive trials, hypokalemia was observed with greater frequency, in a dose-related manner.

In patients with cardiovascular disease, especially those receiving digitalis glycosides, diuretic-induced hypokalemia may be a risk factor for the development of arrhythmias. The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients experiencing a brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes, and in patients receiving concomitant therapy with corticosteroids or ACTH.

Periodic monitoring of serum potassium and other electrolytes is advised in patients treated with DEMADEX.

Precautions

Laboratory Values

Potassium: See WARNINGS.

Calcium

Single doses of DEMADEX increased the urinary excretion of calcium by normal subjects, but serum calcium levels were slightly increased in 4- to 6- weekhypertension trials. In a long-term study of patients with congestive heart failure, the average 1-year change in serum calcium was a decrease of 0.10 mg/dL (0.02 mmol/L). Among 426 patients treated with DEMADEX for an average of 11 months, hypocalcemia was not reported as an adverse event.

Magnesium

Single doses of DEMADEX caused healthy volunteers to increase their urinary excretion of magnesium, but serum magnesium levels were slightly increased in 4- to 6-week hypertension trials. In long-term hypertension studies, the average 1-year change in serum magnesium was an increase of 0.03 mg/dL (0.01 mmol/L). Among 426 patients treated with DEMADEX for an average of 11 months, one case of hypomagnesemia (1.3 mg/dL [0.53 mmol/L]) was reported as an adverse event.

In a long-term clinical study of DEMADEX in patients with congestive heartfailure, the estimated annual change in serum magnesium was an increase of 0.2 mg/dL (0.08 mmol/L), but these data are confounded by the fact that many of these patients received magnesium supplements. In a 4-week study in which magnesium supplementation was not given, the rate of occurrence of serum magnesium levels below 1.7 mg/dL (0.70 mmol/L) was 6% and 9% in the groups receiving 5 mg and 10 mg of DEMADEX, respectively.

Blood Urea Nitrogen (BUN), Creatinine and Uric Acid

DEMADEX produces small dose-related increases in each of these laboratory values. In hypertensive patients who received 10 mg of DEMADEX daily for 6 weeks, the mean increase in blood urea nitrogen was 1.8 mg/dL (0.6 mmol/L), the mean increase in serum creatinine was 0.05 mg/dL (4 mmol/L), and the mean increase in serum uric acid was 1.2 mg/dL (70 mmol/L). Little further change occurred with long-term treatment, and all changes reversed when treatment was discontinued.

Symptomatic gout has been reported in patients receiving DEMADEX, but itsincidence has been similar to that seen in patients receiving placebo.

Glucose

Hypertensive patients who received 10 mg of daily DEMADEX experienced a mean increase in serum glucose concentration of 5.5 mg/dL (0.3 mmol/L) after 6 weeks of therapy, with a further increase of 1.8 mg/dL (0.1 mmol/L) during the subsequent year. In long-term studies in diabetics, mean fasting glucose values were not significantly changed from baseline. Cases of hyperglycemia have been reported but are uncommon.

Serum Lipids

In the controlled short-term hypertension studies in the United States, daily doses of 5 mg, 10 mg, and 20 mg of DEMADEX were associated with increases in total plasma cholesterol of 4, 4, and 8 mg/dL (0.10 to 0.20 mmol/L), respectively. The changes subsided during chronic therapy.

In the same short-term hypertension studies, daily doses of 5 mg, 10 mg and 20 mg of DEMADEX were associated with mean increases in plasma triglyceridesof 16, 13 and 71 mg/dL (0.15 to 0.80 mmol/L), respectively.

In long-term studies of 5 mg to 20 mg of DEMADEX daily, no clinically significant differences from baseline lipid values were observed after 1 year of therapy.

Other

In long-term studies in hypertensive patients, DEMADEX has been associated with small mean decreases in hemoglobin, hematocrit, and erythrocyte count and small mean increases in white blood cell count, platelet count, and serumalkaline phosphatase. Although statistically significant, all of these changes were medically inconsequential. No significant trends have been observed in any liver enzyme tests other than alkaline phosphatase.

Carcinogenesis, Mutagenesis and Impairment of Fertility

No overall increase in tumor incidence was found when torsemide was given to rats and mice throughout their lives at doses up to 9 mg/kg/day (rats) and 32 mg/kg/day (mice). On a body-weight basis, these doses are 27 to 96 times a human dose of 20 mg; on a body-surface-area basis, they are 5 to 8 times this dose. In the rat study, the high-dose female group demonstrated renal tubularinjury, interstitial inflammation, and a statistically significant increase in renal adenomas and carcinomas. The tumor incidence in this group was, however, not much higher than the incidence sometimes seen in historical controls. Similar signs of chronic non-neoplastic renal injury have been reported in high-dose animal studies of other diuretics such as furosemide and hydrochlorothiazide.

No mutagenic activity was detected in any of a variety of in vivo and in vitro tests of torsemide and its major human metabolite. The tests included the Ames testin bacteria (with and without metabolic activation), tests for chromosomeaberrations and sister-chromatid exchanges in human lymphocytes, tests for various nuclear anomalies in cells found in hamster and murine bone marrow, tests for unscheduled DNA synthesis in mice and rats, and others.

In doses up to 25 mg/kg/day (75 times a human dose of 20 mg on a body- weight basis; 13 times this dose on a body-surface-area basis), torsemide had no adverse effect on the reproductive performance of male or female rats.

Pregnancy

Pregnancy Category B.

There was no fetotoxicity or teratogenicity in rats treated with up to 5 mg/kg/day of torsemide (on a mg/kg basis, this is 15 times a human dose of 20 mg/day; on a mg/m² basis, the animal dose is 10 times the human dose), or in rabbits, treated with 1.6 mg/kg/day (on a mg/kg basis, 5 times the human dose of 20 mg/kg/day; on a mg/m² basis, 1.7 times this dose). Fetal and maternal toxicity(decrease in average body weight, increase in fetal resorption and delayed fetalossification) occurred in rabbits and rats given doses 4 (rabbits) and 5 (rats) times larger. Adequate and well-controlled studies have not been carried out in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

The effect of DEMADEX on labor and delivery is unknown.

Nursing Mothers

It is not known whether DEMADEX is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when DEMADEX is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Administration of another loop diuretic to severely premature infants with edemadue to patent ductus arteriosus and hyaline membrane disease has occasionally been associated with renal calcifications, sometimes barely visible on X-ray but sometimes in staghorn form, filling the renal pelves. Some of these calculi have been dissolved, and hypercalciuria has been reported to have decreased, when chlorothiazide has been coadministered along with the loop diuretic. In other premature neonates with hyaline membrane disease, another loop diuretic has been reported to increase the risk of persistent patent ductus arteriosus, possibly through a prostaglandin-E- mediated process. The use of DEMADEX in such patients has not been studied.

Geriatric Use

Of the total number of patients who received DEMADEX in United States clinical studies, 24% were 65 or older while about 4% were 75 or older. No specific age-related differences in effectiveness or safety were observed between younger patients and elderly patients.

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Overdose

There is no human experience with overdoses of DEMADEX, but the signs and symptoms of overdosage can be anticipated to be those of excessive pharmacologic effect: dehydration, hypovolemia, hypotension, hyponatremia,hypokalemia, hypochloremic alkalosis, and hemoconcentration. Treatment of overdosage should consist of fluid and electrolyte replacement.

Laboratory determinations of serum levels of torsemide and its metabolites are not widely available.

No data are available to suggest physiological maneuvers (eg, maneuvers to change the pH of the urine) that might accelerate elimination of torsemide and its metabolites. Torsemide is not dialyzable, so hemodialysis will not accelerate elimination.

Contraindications

DEMADEX is contraindicated in patients with known hypersensitivity to DEMADEX or to sulfonylureas.

DEMADEX is contraindicated in patients who are anuric.

Torsemide - Demadex

Torsemide - Demadex - Diuretic for Generalized Edema

Part One

One of the most commonly prescribed medicines for

fluid retention (generalized edema/ swelling)

DEMADEX (torsemide) is a diuretic of the pyridine-sulfonylurea class.

DEMADEX is indicated for the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Use of torsemide has been found to be effective for the treatment of edema associated with chronic renal failure.Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.

DEMADEX intravenous injection is indicated when a rapid onset of iuresis is desired or when oral administration is impractical.

DEMADEX is indicated for the treatment of hypertension alone or in combination with other antihypertensive agents.

Dosage and Administration

General

DEMADEX tablets may be given at any time in relation to a meal, as convenient. Special dosage adjustment in the elderly is not necessary.

Because of the high bioavailability of DEMADEX, oral and intravenous doses are therapeutically equivalent, so patients may be switched to and from the intravenous form with no change in dose. DEMADEX intravenous injection should be administered either slowly as a bolus over a period of 2 minutes or administered as a continuous infusion.

If DEMADEX is administered through an IV line, it is recommended that, as with other IV injections, the IV line be flushed with Normal Saline (Sodium Chloride Injection, USP) before and after administration. DEMADEX injection is formulated above pH 8.3. Flushing the line is recommended to avoid the potential for incompatibilities caused by differences in pH which could be indicated by color change, haziness or the formation of a precipitate in the solution.

If DEMADEX is administered as a continuous infusion, stability has been demonstrated through 24 hours at room temperature in plastic containers for the following fluids and concentrations:

200 mg DEMADEX (10 mg/mL) added to:

250 mL Dextrose 5% in water
250 mL 0.9% Sodium Chloride
500 mL 0.45% Sodium Chloride

50 mg DEMADEX (10 mg/mL) added to:

500 mL Dextrose 5% in water
500 mL 0.9% Sodium Chloride
500 mL 0.45% Sodium Chloride

Before administration, the solution of DEMADEX should be visually inspected for discoloration and particulate matter. If either is found, the ampul should not be used.

Congestive Heart Failure

The usual initial dose is 10 mg or 20 mg of once-daily oral or intravenous DEMADEX. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200 mg have not been adequately studied.

Chronic Renal Failure

The usual initial dose of DEMADEX is 20 mg of once-daily oral or intravenous DEMADEX. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200 mg have not been adequately studied.

Hepatic Cirrhosis

The usual initial dose is 5 mg or 10 mg of once-daily oral or intravenous DEMADEX, administered together with an aldosterone antaagonist or a potassium-sparing diuretic. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 40 mg have not been adequately studied.

Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.

Hypertension

The usual initial dose is 5 mg once daily. If the 5 mg dose does not provide adequate reduction in blood pressure within 4 to 6 weeks, the dose may be increased to 10 mg once daily. If the response to 10 mg is insufficient, an additional antihypertensive agent should be added to the treatment regimen.

105 (for 5 mg, 10 mg, 20 mg, or 100 mg, respectively). On the opposite side, the tablet is debossed with 5, 10, 20, or 100 to indicate the dose.

DEMADEX for intravenous injection is supplied in clear ampuls containing 2 mL (20 mg, NDC 0004-0267-06) or 5 mL (50 mg, NDC 0004-0268-06) of a 10 mg/mL sterile solution. The ampuls are supplied in boxes of 10.

Side Effects

At the time of approval, DEMADEX had been evaluated for safety in approximately 4000 subjects: over 800 of these subjects received DEMADEX for at least 6 months, and over 380 were treated for more than 1 year. Among these subjects were 564 who received DEMADEX during United States-based trials in which 274 other subjects received placebo.

The reported side effects of DEMADEX were generally transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effects occurred in 3.5% of United States patients treated with DEMADEX and in 4.4% of patients treated with placebo. In studies conducted in the United States and Europe, discontinuation rates due to side effects were 3.0% (38/1250) with DEMADEX and 3.4% (13/380) with furosemide in patients with congestive heart failure, 2.0% (8/409) with DEMADEX and 4.8% (11/230) with furosemide in patients with renal insufficiency, and 7.6% (13/170) with DEMADEX and 0% (0/33) with furosemide in patients withcirrhosis.

The most common reasons for discontinuation of therapy with DEMADEX were (in descending order of frequency) dizziness, headache, nausea, weakness, vomiting, hyperglycemia, excessive urination, hyperuricemia, hypokalemia, excessive thirst, hypovolemia, impotence, esophageal hemorrhage, anddyspepsia. Dropout rates for these adverse events ranged from 0.1% to 0.5%.

The daily doses of DEMADEX used in these trials ranged from 1.25 mg to 20 mg, with most patients receiving 5 mg to 10 mg; the duration of treatment ranged from 1 to 52 days, with a median of 41 days. Of the side effects listed in the table, only "excessive urination" occurred significantly more frequently in patients treated with DEMADEX than in patients treated with placebo. In the placebo-controlled hypertension studies whose design allowed side-effect rates to be attributed to dose, excessive urination was reported by 1% of patients receiving placebo, 4% of those treated with 5 mg of daily DEMADEX, and 15% of those treated with 10 mg. The complaint of excessive urination was generally not reported as an adverse event among patients who received DEMADEX for cardiac, renal, or hepatic failure.

Serious adverse events reported in the clinical studies for which a drug relationship could not be excluded were atrial fibrillation, chest pain, diarrhea, digitalis intoxication, gastrointestinal hemorrhage, hyperglycemia, hyperuricemia, hypokalemia, hypotension, hypovolemia, shunt thrombosis, rash,rectal bleeding, syncope, and ventricular tachycardia.

Angioedema has been reported in a patient exposed to DEMADEX who was later found to be allergic to sulfa drugs.

Of the adverse reactions during placebo-controlled trials listed without taking into account assessment of relatedness to drug therapy, arthritis and various other nonspecific musculoskeletal problems were more frequently reported in association with DEMADEX than with placebo, even though gout was somewhat more frequently associated with placebo. These reactions did not increase in frequency or severity with the dose of DEMADEX. One patient in the group treated with DEMADEX withdrew due to myalgia, and one in the placebo group withdrew due to gout.

Drug Interactions

In patients with essential hypertension, DEMADEX has been administered together with beta-blockers, ACE inhibitors, and calcium-channel blockers. In patients with congestive heart failure, DEMADEX has been administered together with digitalis glycosides, ACE inhibitors, and organic nitrates. None of these combined uses was associated with new or unexpected adverse events.

Torsemide does not affect the protein binding of glyburide or of warfarin, theanticoagulant effect of phenprocoumon (a related coumarin derivative), or the pharmacokinetics of digoxin or carvedilol (a vasodilator/beta-blocker). In healthy subjects, coadministration of DEMADEX was associated with significant reduction in the renal clearance of spironolactone, with corresponding increases in the AUC. However, clinical experience indicates that dosage adjustment of either agent is not required.

Because DEMADEX and salicylates compete for secretion by renal tubules, patients receiving high doses of salicylates may experience salicylate toxicity when DEMADEX is concomitantly administered. Also, although possible interactions between torsemide and nonsteroidal anti-inflammatory agents (including aspirin) have not been studied, coadministration of these agents with another loop diuretic (furosemide) has occasionally been associated with renal dysfunction.

The natriuretic effect of DEMADEX (like that of many other diuretics) is partially inhibited by the concomitant administration of indomethacin. This effect has been demonstrated for DEMADEX under conditions of dietary sodium restriction (50 mEq/day) but not in the presence of normal sodium intake (150 mEq/day).

The pharmacokinetic profile and diuretic activity of torsemide are not altered by cimetidine or spironolactone. Coadministration of digoxin is reported to increase the area under the curve for torsemide by 50%, but dose adjustment of DEMADEX is not necessary.

Concomitant use of torsemide and cholestyramine has not been studied in humans but, in a study in animals, coadministration of cholestyramine decreased the absorption of orally administered torsemide. If DEMADEX and cholestyramine are used concomitantly, simultaneous administration is not recommended.

Coadministration of probenecid reduces secretion of DEMADEX into the proximal tubule and thereby decreases the diuretic activity of DEMADEX.

Other diuretics are known to reduce the renal clearance of lithium, inducing a high risk of lithium toxicity, so coadministration of lithium and diuretics should be undertaken with great caution, if at all. Coadministration of lithium and DEMADEX has not been studied.

Other diuretics have been reported to increase the ototoxic potential of aminoglycoside antibiotics and of ethacrynic acid, especially in the presence of impaired renal function. These potential interactions with DEMADEX have not been studied.

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Abdominoscrotal hydrocele with leg edema in a 4-month-old boy

Abdominoscrotal hydrocele with leg edema in a 4-month-old boy

Prog Urol. 2009 Oct

Faure A, Bouali O, Chaumoitre K, Louka B, Alessandrini P, Merrot T.

Service de chirurgie pédiatrique, hôpital Nord, AP-HM, université de la Méditerranée, chemin des Bourrelly, 13915 Marseille cedex 20, France.

We present a case of a 4-month-old boy with a right abdominoscrotal hydrocele associated to a compression of the femoral triangle, causing an unilateral leg edema. Abdominoscrotal ultrasound revealed a fluid collection with abdominal and scrotal components, communicating through the deep inguinal ring. Sagittal views of magnetic resonance imaging (MRI) showed a dumbbell-shaped hydrocele and the angio-MRI venous sequences confirmed the compression of the right iliac vessels.

Curative treatment was surgical through an inguinal approach and consisted in high ligation of the processus vaginalis and hydrocelectomy. Abdominoscrotal hydrocele is an uncommon pathology, which rarely occurs in pediatric population. This diagnosis should be discussed when a cystic abdominal mass is associated to an ipsilateral scrotal hydrocele. The abdominal component of the hydrocele can result in compression of adjacent structures (iliac vessels, ureter). Surgical treatment is recommended. Epididymal and testicular abnormalities are frequently described, as in our observation, and the effects on the future fertility are unknown.

Elsevier/Science Direct

Feasibility of treatment of lower limb edema with calf muscle pump stimulation in chronic heart failure.

Feasibility of treatment of lower limb edema with calf muscle pump stimulation in chronic heart failure.

Eur J Cardiovasc Nurs. 2009 Aug 31

Pierce C, McLeod KJ.

Decker School of Nursing, Binghamton University, United States; Department of Bioengineering, Binghamton University, United States.

BACKGROUND: Persons with chronic heart failure may exhibit a decrease in functional ability related to lower extremity edema in spite of optimal diuretic therapy and salt restrictions.

AIM: The aim of this pilot prospective clinical study was to test the feasibility of using exogenous calf muscle pump stimulation to decrease lower leg edema and thus improve functional status and quality of life.

METHODS: Six subjects entered into this study and agreed to use the intervention 30min/day for one month. DXA was used to assess lower extremity composition.

RESULTS: Device use averaged approximately 1h/day and resulted in a reduction in the lean mass of the legs of 0.5kg (range=0.08-1.0L; p=0.03). Linear regression analysis of reduction of lower limb edema against daily usage suggests that increased utilization of calf muscle pump stimulation was associated with increased water losses, although this trend was not significant (R(2)=0.4, p=0.18).

CONCLUSION: This pilot indicates that exogenous calf muscle pump stimulation could be a useful and safe addition to the patients' treatment regimes, but further studies testing a more typical population with heart failure is warranted.

Science Direct

Mesoglycan

Mesoglycan

Description

Mesoglycan is a mucopolysaccharide complex that is extracted from calf aorta or synthetically created and taken in pill or capsule form as a dietary supplement. Mucopolysaccharides are long molecular chains of sugar. They are used by the body in the building of connective tissues, such as cartilage, tendons, and ligaments. The substance is related to the blood-thinning drug heparin, and the supplements glucosamine and chondroitin. Both are used to treat joint pain and arthritis.

What other names is Mesoglycan known by?

Aortic Glycosaminoglycans, Aortic GAGs, Glycosaminoglycans, Heparinoid Fraction, Heparinoids, Mucopolysaccharide, Sulfomucopolysaccharide.

What is Mesoglycan?

Mesoglycan is a substance obtained from cow lung or blood vessels (aorta), or pig intestine.

Possibly Effective for...

• Treating poor circulation that can lead to varicose veins and other conditions.
• Treating leg ulcers.
• Reducing blood levels of certain fats called triglycerides.
• Reducing pain when walking in people with a disease called peripheral arterial disease.
• Improving thinking and quality of life in people with limited blood flow to the brain (cerebrovascular disease).

Possibly Ineffective for...

• Preventing blood clots in the legs and lungs (deep vein thrombosis and pulmonary embolism).
• Treating stroke.

Insufficient Evidence to Rate Effectiveness for...

• Hemorrhoids, atherosclerosis (a type of heart disease), inflammation of blood vessels (vasculitis), and other conditions.

rxlist.com

Pharmacological treatment of mechanical edema: a randomized controlled trial about the effects of mesoglycan.

Pharmacological treatment of mechanical edema: a randomized controlled trial about the effects of mesoglycan.

Eur J Phys Rehabil Med. 2009 Mar

Recovery and Rehabilitation Agency, University Hospital of Careggi, Florence, Italy

AIM: Mechanical edema (MO) is frequently found in a lot of the lower extremities' orthopedic diseases. In absence of deep vein thrombosis, MO is caused by the change in the dynamics of calf muscle pump with venous hypertension and by the change in capillary permeability which offsets the extra-vascular fluid balance resulting in edema formation. The correct treatment includes specific training for musculo-skeletal and gait recovery, together with medical treatment focused on venous endothelium. Little information is available about pharmacological treatment of this condition. Some studies suggest the efficacy of mesoglycan in venous pathology. Aim of this study was to evaluate the clinical efficacy of the pharmacological treatment (mesoglycan 50 mg p.o., twice a day) in patients affected by MO.

METHODS: Forty-four patients with MO, aged 20-89 years, were randomized in two treatment groups: specific physiotherapy (Fkt) alone or physiotherapy plus mesoglycan 50 mg twice a day, per os. The patients were evaluated before treatment (t0), and after 1 month of treatment (t1), measuring ankle joint range of motion (degrees), calf circumference and malleolar circumference (cm), pain Borg CR10 Scale and adapted lymphedema Weiss Scale. Statistical analysis was performed by the Pearson's c2 test and the Mann-Whitney-Wilcoxon test.

RESULTS: At the final evaluation of the objective and subjective parameters, the mesoglycan effect combined to the Fkt provided statistical differences on nearly all the parameters in comparison with the patients randomised to Fkt alone.

CONCLUSIONS: The present study suggest that mesoglycan treatment (50 mg p.o., twice a day) can improve the recovery of MO, and it is well tolerated by the patients. Specific physiotherapy remains the first treatment for the recovery of both muscular pump and correct walking, but the optimal treatment of MO seems to be a synergic approach, including both pharmacological and mobilization programs.

Minerva Medica

Efficacy of intravitreal bevacizumab (Avastin) for short-term treatment of diabetic macular edema.

Efficacy of intravitreal bevacizumab (Avastin) for short-term treatment of diabetic macular edema.
Nagasawa T, Naito T, Matsushita S, Sato H, Katome T, Shiota H.
Department of Ophthalmology, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan.

PURPOSE: To report the efficacy of intravitreal injections of bevacizumab for diabetic macular edema (DME) in the short-term.

DESIGN: Retrospective, noncomparative, interventional case series.

METHODS: Medical records of 20 eyes of 19 patients who underwent intravitreal injections of bevacizumab for persistent diabetic macular edema were reviewed retrospectively. All eyes received intravitreal injections of bevacizumab (1.25 mg/0.05 ml). The clinical course of best-corrected visual acuity (BCVA) using a logarithm of the minimum angle of resolution chart, and averaged foveal retinal thickness using an optical coherence tomography (OCT) were monitored for up to four weeks after the injection.

RESULTS: BCVA at one week improved by two lines or more in six eyes (30%) and in nine eyes (45%) at four weeks. However, no significant improvement in the mean BCVA from baseline was observed at one week (P>0.05) and four weeks (P>0.05). Mean retinal thicknesses (RT) were 411+/-170 mum at baseline, 349+/-102 microm at one week after the injection (P<0.05),>0.05). One week after the injection, significant regression of macular edema was seen. However, recurrence occurred at four weeks. No complications such as severe vision loss, endophthalmitis, or systemic events developed.

CONCLUSION: No changes in BCVA and RT were observed in the short-term observation after the intravitreal injection of bevacizumab for DME.

Journal of Medical Investigation

Metolazone

Metolazone

GENERIC NAME: METOLAZONE - ORAL (me-TOLE-a-zone)
BRAND NAME(S): Zaroxolyn

One of the old fashion but quite effective diuretics in the treatment of generalized edema is a medicine called metolazone. Presently, after experiencing severe lymphatic failure with bi-lateral lung edema, a history of lymphoma and contending with hereditary lymphedema radiology tests indicate almost no lymphatic flow through the thoracic duct or through the right side lymphatic drainage fields. Clearly, it is a matter of life for me to be able to somehow get rid of the massive amounts of fluid that is collecting in my body.


I must add however, that unless there is a life threatening co-morbidity, lymphedema patients should not be treated with diuretics.

Very recently, my doctor put me on metolazone with incredible results.

What is metolazone?

Metolazone is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

Metolazone treats fluid retention (edema) in people with congestive heart failure, or a kidney disorder such as nephrotic syndrome. This medication is also used to treat high blood pressure (hypertension).

Metolazone may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about metolazone?

Do not use this medication if you are unable to urinate, or if you have severe liver disease.

Before using this medication, tell your doctor if you have liver disease, kidney disease, asthma, allergies, gout, diabetes, or an allergy to sulfa drugs.Avoid drinking alcohol, which can increase some of the side effects of metolazone.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

There are many other medicines that can interact with metolazone. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

If you are being treated for high blood pressure, keep using this medication even if you feel fine.

High blood pressure often has no symptoms.

What should I discuss with my doctor before taking metolazone?

Do not use this medication if you are allergic to metolazone, or if you have:
severe liver disease; or if you are unable to urinate.

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before using metolazone, tell your doctor if you have:

kidney disease;
liver disease;
gout;
diabetes; or

an allergy to sulfa drugs.FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Metolazone can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take metolazone?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

To be sure this medication is not causing harmful effects, your blood will need to be tested on a regular basis. Do not miss any scheduled appointments.

Your blood and urine may both be tested if you have been vomiting or are dehydrated.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking metolazone. You may need to stop using the medicine for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel fine. High blood pressure often has no symptoms.Store the tablets at room temperature away from heat, light, and moisture.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include nausea, weakness, dizziness, dry mouth, thirst, muscle pain or weakness, feeling light-headed, or fainting.

What should I avoid while taking metolazone?

Avoid drinking alcohol, which can increase some of the side effects of metolazone.

Avoid using other medicines that make you light-headed (narcotic pain medication, muscle relaxers, and medicine for seizures). They can add to the side effects of metolazone. Tell your doctor if you regularly use any of these medicines, or any other blood pressure medications.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.


Drugs.com

HOW TO USE: Take this medication by mouth with or without food, usually once daily, or as directed by your doctor. The dosage is based on your medical condition and response to therapy. It is best to take this medication early in the day, before 4-6PM, to prevent having to wake up during the night to urinate. Consult your doctor or pharmacist if you have questions about your dosing schedule. Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day as directed. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick. Do not stop taking this medication without consulting your doctor. It may take up to 3-6 weeks to see a lowering of your blood pressure. Cholestyramine and colestipol can decrease the absorption of metolazone. If you are taking either of these drugs, separate metolazone from cholestyramine by at least 4 hours and from colestipol by at least 2 hours. Different brands of metolazone may not be equal. Do not switch to another brand without your doctor's approval. If your condition persists or worsens, contact your doctor or pharmacist.

SIDE EFFECTS: Dizziness, lightheadedness, headache, blurred vision, loss of appetite, stomach upset, diarrhea, or constipation may occur as your body adjusts to the medication. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. This medication may lead to excessive loss of body water and minerals (including potassium). Tell your doctor immediately if you have any of these unlikely but serious symptoms of dehydration or mineral loss: muscle cramps or weakness, confusion, severe dizziness, unusual dry mouth or thirst, nausea or vomiting, fast/irregular heartbeat, unusual decrease in the amount of urine, fainting, seizures. Tell your doctor immediately if any of these unlikely but serious side effects occur: numbness/tingling of the arms/legs, decreased sexual ability, chest pain. Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: persistent sore throat or fever, easy bleeding or bruising, stomach/abdominal pain, persistent nausea/vomiting, yellowing of eyes/skin. A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist.

PRECAUTIONS: Before taking metolazone, tell your doctor or pharmacist if you are allergic to it; or to sulfa medications; or if you have any other allergies. This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe kidney disease (inability to make urine or anuria). Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, untreated mineral imbalance (e.g., sodium, potassium), gout, lupus. If you have diabetes, metolazone may worsen control of blood glucose levels. Monitor your blood glucose levels regularly and inform your doctor of the results. This drug may reduce the potassium levels in your blood. Ask your doctor about adding potassium to your diet. A potassium supplement may be prescribed by your doctor. This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors. Before having surgery, tell your doctor or dentist that you are taking this medication. This drug may make you dizzy or cause blurred vision; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages. To minimize dizziness and lightheadedness, get up slowly when rising from a seated or lying position. Caution is advised when using this drug in the elderly because they may be more sensitive to its effects, especially dizziness. Metolazone should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor. This drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also the How to Use section. This drug should not be used with the following medications because very serious interactions may occur: cisapride. If you are currently using any of these medications, tell your doctor or pharmacist before starting metolazone. Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: cholestyramine, colestipol, corticosteroids (e.g., prednisone), diazoxide, digoxin, lithium, nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, indomethacin). Check the labels on all your medicines (e.g., cough-and-cold products, diet aids) because they may contain ingredients that could increase your blood pressure. Ask your pharmacist about the safe use of those products. This product can affect the results of certain lab tests (e.g., parathyroid function tests). Make sure laboratory personnel and your doctors know you use this drug. Do not start or stop any medicine without doctor or pharmacist approval.

MedicineNet.com

Leg edema with deep venous thrombosis-like symptoms as an unusual complication of occult bladder distension and right May-Thurner syndrome in a stroke

Leg edema with deep venous thrombosis-like symptoms as an unusual complication of occult bladder distension and right May-Thurner syndrome in a stroke patient: a case report.

Arch Phys Med Rehabil. 2009 May

Im S, Lim SH, Chun HJ, Ko YJ, Yang BW, Kim HW.
Department of Rehabilitation Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-ku, Seoul, Republic of Korea.

Overt bladder distension can compress the iliac vessels and result in lower extremity swelling mimicking deep venous thrombosis (DVT). This phenomenon has been reported in patients with bladder outlet obstruction due to prostatism but no report has been made in relation to poststroke urinary retention (UR). The authors experienced a rare case of abrupt leg edema with DVT-like symptoms due to iliac vein compression by an overdistended bladder that had developed after cerebrovascular stroke. A 74-year-old woman with left striatocapsular infarction and situs inversus presented with severe right leg swelling. Imaging studies revealed external compression of the right iliac veins by an overdistended bladder and underlying May-Thurner syndrome (MTS). The presence of situs inversus totalis resulted in the rare clinical finding of a right-sided MTS. The patient's symptoms were largely attributable to external compression of right iliac veins by bladder distension and they resolved completely after prompt bladder drainage. Follow-up imaging findings showed complete regression of right external iliac vein stenosis. This case provides the first description of lower extremity swelling manifest as an unusual complication from UR in a stroke patient. Proper and strict bladder screening with appropriate management should be implemented as important therapeutic components during the rehabilitative management of stroke patients.

Abbreviations: CT, computed tomography; DVT, deep venous thrombosis; MTS, May-Thurner syndrome; UR, urinary retention

Elsevier

A 62-year-old woman with non-pitting leg oedema

A 62-year-old woman with non-pitting leg oedema
Tidsskr Nor Laegeforen. 2009 Apr 16

Bergersen TK, Mørk C.
kristin.bergersen@rikshospitalet.no

A patient presented with non-pitting lymphoedema of the legs and finger clubbing. A skin biopsy showed epidermal hyperkeratosis and abundant mucinous material (Alcian blue positive) in reticular dermis. Treatment (radioactive iodine) for Grave's disease (with exophthalmus) 20 years ago, raised suspicion of thyroid dermopathy. Together, these three extrathyroidal manifestations of Graves' disease are typical of the EMO syndrome. In addition, the patient had elevated serum concentrations of thyroid-stimulating hormone receptor autoantibodies. Autoimmune mechanisms are involved in the stimulation of fibroblasts and the production of large amounts of mucin. Pretibial myxoedema relates to scars, mechanical factors, and dependent position. Lack of steroid treatment during radioactive iodine therapy and smoking, may have exacerbated the thyroid dermopathy in this case. Awareness of pretibial myxoedema as a late autoimmune manifestation of Graves' disease, may contribute to earlier diagnosis and correct treatment.

Full text Article

.[Article in Portuguese, English]

Post -tracheal extubation pulmonary oedema - Case report

Castro MD, Chaves P, Canas M, Moedas ML.
Interna de Anestesiologia, Hospital de S. António dos Capuchos, Centro Hospitalar de Lisboa Central - EPE (CHLC - EPE).

Negative pressure pulmonary oedema is an uncommon complication of traqueal extubation ( approximately 0,1%) mostly caused by acute upper airway obs truction. Upper airway obstruction from glottis closure leads to marked inspiratory effort, which generates negative intrathoracic pressure transmitting to pulmonary interstitium, and inducing fluid transudation from pulmonary capillary bed1 -5. We report a case of post- -extubation pulmonary oedema in a fifteen years old patient, submitted to surgery following traumatic amputation of his left leg. We review the pathophysiology, radiological findings, potential risk factors and preventive measures of this post -anaesthetic respiratory complication. Rev Port Pneumol 2009; XV (3): 537-541 Key-words: Post -extubation pulmonary oedema, upper airway obstruction, laryngospasm, intra -thoracic negative pressure.

PMID: 19401801 [PubMed - as supplied by publisher]

Persistent Subcutaneous Oedema and Aseptic Fatty Tissue Necrosis after Using Octenisept(R).

Persistent Subcutaneous Oedema and Aseptic Fatty Tissue Necrosis after Using Octenisept(R).
Eur J Pediatr Surg. 2009 Jun

Schupp CJ, Holland-Cunz S.
1Division of Pediatric Surgery, University Hospital Heidelberg, Heidelberg, Germany.

INTRODUCTION: Wound management and the prevention and treatment of tissue infections are part of daily routine. Octenisept ((R)) (Schülke & Mayr), an antiseptic with a broad antimicrobiological effect, is widely used for various indications. This paper reports prolonged oedema and tissue swelling after treatment of deep wounds with Octenisept ((R)) in three children.

CASE REPORTS: Three paediatric patients, aged between 2 months and 4 years, were treated with Octenisept ((R)) in different hospitals. One initially presented with an abscess of the gluteal area, two with deep wounds of the cheek following injury with a wooden stick. The wounds were cleaned and washed out with Octenisept ((R)). Adequate drainage was in place at all times.

COMMON FINDINGS: We observed aseptic, non painful subcutaneous tissue swelling and oedema in all three cases after wound lavage with Octenisept ((R)). This occurred shortly after the wound was initially treated and lasted for weeks until the symptoms slowly declined. It was not accompanied by persistent general infection parameters. A biopsy taken from one patient demonstrated an aseptic inflammatory reaction and oedema of the subcutaneous tissue, with partial tissue necrosis. Neither surgical revision nor antibiotic therapy brought any improvement.

CONCLUSIONS: Retrospectively, one can consider these occurrences as a consequence of the use of Octenisept ((R)), since the changes are consistent with those described by Schülke & Mayr when Octenisept ((R)) was accidentally administered by subcutaneous injection or under pressure to flush deep hand stab wounds that were not drained. The underlying pathobiological mechanism remains unclear. Hence, we recommend not to apply Octenisept ((R)) in any wound cavity until further investigation has taken place. If aseptic fatty tissue necrosis and oedema develop after using Octenisept ((R)), further surgical intervention or antibiotic treatment will not give any benefit. Changes subside slowly. So far, adequate treatment is not available.

Thieme/eJournals