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American Family Physician Jul 2013Edema is an accumulation of fluid in the interstitial space that occurs as the capillary filtration exceeds the limits of lymphatic drainage, producing noticeable... (Review)
Review
Edema is an accumulation of fluid in the interstitial space that occurs as the capillary filtration exceeds the limits of lymphatic drainage, producing noticeable clinical signs and symptoms. The rapid development of generalized pitting edema associated with systemic disease requires timely diagnosis and management. The chronic accumulation of edema in one or both lower extremities often indicates venous insufficiency, especially in the presence of dependent edema and hemosiderin deposition. Skin care is crucial in preventing skin breakdown and venous ulcers. Eczematous (stasis) dermatitis can be managed with emollients and topical steroid creams. Patients who have had deep venous thrombosis should wear compression stockings to prevent postthrombotic syndrome. If clinical suspicion for deep venous thrombosis remains high after negative results are noted on duplex ultrasonography, further investigation may include magnetic resonance venography to rule out pelvic or thigh proximal venous thrombosis or compression. Obstructive sleep apnea may cause bilateral leg edema even in the absence of pulmonary hypertension. Brawny, nonpitting skin with edema characterizes lymphedema, which can present in one or both lower extremities. Possible secondary causes of lymphedema include tumor, trauma, previous pelvic surgery, inguinal lymphadenectomy, and previous radiation therapy. Use of pneumatic compression devices or compression stockings may be helpful in these cases.
Topics: Edema; Humans; Lymphedema; Physical Examination; Venous Insufficiency; Venous Thrombosis
PubMed: 23939641
DOI: No ID Found -
American Family Physician Jun 2005Edema is the result of an imbalance in the filtration system between the capillary and interstitial spaces. The kidneys play a key role in regulating extracellular fluid... (Review)
Review
Edema is the result of an imbalance in the filtration system between the capillary and interstitial spaces. The kidneys play a key role in regulating extracellular fluid volume by adjusting sodium and water excretion. Major causes of edema include venous obstruction, increased capillary permeability, and increased plasma volume secondary to sodium and water retention. A systematic approach is warranted to determine the underlying diagnosis. Treatment includes sodium restriction, diuretic use, and appropriate management of the underlying disorder. Leg elevation may be helpful in some patients. Loop diuretics often are used alone or in combination. In patients with New York Heart Association class III and IV congestive heart failure, spironolactone has been found to reduce morbidity and mortality rates. In patients with cirrhosis, ascites is treated with paracentesis and spironolactone. Dihydropyridine-induced edema can be treated with an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. Lymphedema occurs when a protein-rich fluid accumulates in the interstitium. Compression garments and range-of-motion exercises may be helpful in patients with this condition.
Topics: Angiotensin-Converting Enzyme Inhibitors; Diet, Sodium-Restricted; Diuretics; Edema; Exercise Therapy; Humans; Paracentesis
PubMed: 15952439
DOI: No ID Found -
Cell May 2020Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials,...
Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials, meaning that symptom management is the only treatment option. The water channel protein aquaporin-4 (AQP4) is expressed in astrocytes and mediates water flux across the blood-brain and blood-spinal cord barriers. Here we show that AQP4 cell-surface abundance increases in response to hypoxia-induced cell swelling in a calmodulin-dependent manner. Calmodulin directly binds the AQP4 carboxyl terminus, causing a specific conformational change and driving AQP4 cell-surface localization. Inhibition of calmodulin in a rat spinal cord injury model with the licensed drug trifluoperazine inhibited AQP4 localization to the blood-spinal cord barrier, ablated CNS edema, and led to accelerated functional recovery compared with untreated animals. We propose that targeting the mechanism of calmodulin-mediated cell-surface localization of AQP4 is a viable strategy for development of CNS edema therapies.
Topics: Animals; Aquaporin 4; Astrocytes; Brain; Brain Edema; Calmodulin; Central Nervous System; Edema; Male; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Trifluoperazine
PubMed: 32413299
DOI: 10.1016/j.cell.2020.03.037 -
Ugeskrift For Laeger Apr 2023Pedal oedema is a well-known adverse effect of amlodipine, but significantly less frequent if only half of the maximum recommended dosage is used. Diuretics are... (Review)
Review
Pedal oedema is a well-known adverse effect of amlodipine, but significantly less frequent if only half of the maximum recommended dosage is used. Diuretics are ineffective. To cause as few side effects as possible, options for managing are prioritised in this review: Reduce dosage, switch to lercanidipine/lacidipine, switch to another group, add/increase dosage of an ACE-inhibitor/angiotensin II-receptor blocker, administer at night, or switch to verapamil/diltiazem. Non-pharmacologic actions or observation may be considered when the oedemas are mild and not bothersome.
Topics: Humans; Amlodipine; Calcium Channel Blockers; Hypertension; Ankle; Edema; Drug-Related Side Effects and Adverse Reactions
PubMed: 37114573
DOI: No ID Found -
British Journal of Clinical Pharmacology Aug 2021Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca... (Review)
Review
Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often noninflammatory and bilateral, some drugs are associated with peripheral oedema that is readily erythematous (eg, pemetrexed) or unilateral (eg, sirolimus). Thus, drug-induced peripheral oedema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory oedema), sodium/water retention (renal oedema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability oedema). The underlying mechanism has significant impact on treatment efficacy. The purpose of this review is to provide a comprehensive analysis of the main causative drugs by illustrating each pathophysiological mechanism and their management through an example of a drug.
Topics: Edema; Heart Failure; Humans; Lymphedema; Pharmaceutical Preparations; Vasodilation
PubMed: 33506982
DOI: 10.1111/bcp.14752 -
Pharmacology & Therapeutics Sep 2017Transient Receptor Potential Vanilloid 4 (TRPV4) is a broadly expressed, polymodally gated ion channel that plays an important role in many physiological and... (Review)
Review
Transient Receptor Potential Vanilloid 4 (TRPV4) is a broadly expressed, polymodally gated ion channel that plays an important role in many physiological and pathophysiological processes. TRPV4 knockout mice and several synthetic pharmacological compounds that selectively target TRPV4 are now available, which has allowed detailed investigation in to the therapeutic potential of this ion channel. Results from animal studies suggest that TRPV4 antagonism has therapeutic potential in oedema, pain, gastrointestinal disorders, and lung diseases such as cough, bronchoconstriction, pulmonary hypertension, and acute lung injury. A lack of observed side-effects in vivo has prompted a first-in-human trial for a TRPV4 antagonist in healthy participants and stable heart failure patients. If successful, this would open up an exciting new area of research for a multitude of TRPV4-related pathologies. This review will discuss the known roles of TRPV4 in disease, and highlight the possible implications of targeting this important cation channel for therapy.
Topics: Animals; Edema; Gastrointestinal Diseases; Humans; Lung Diseases; Pain; TRPV Cation Channels
PubMed: 28202366
DOI: 10.1016/j.pharmthera.2017.02.019 -
ESC Heart Failure Oct 2020The presence of chronic heart failure (CHF) results in a significant risk of leg oedema. Medical compression (MC) treatment is one of the basic methods of leg oedema... (Review)
Review
The presence of chronic heart failure (CHF) results in a significant risk of leg oedema. Medical compression (MC) treatment is one of the basic methods of leg oedema elimination in patients with chronic venous disease and lymphedema, but it is not routinely considered in subjects with CHF-related swelling. In the study, an overview of the current knowledge related to the benefits and risk of using MC in the supportive treatment of leg oedema in CHF patients is presented. The available studies dedicated the comprehensive management of leg swelling using MC in CHF patients published in the English language literature till December 2019 were evaluated in term of the treatment efficacy and safety. In studies performed on CHF populations, manual lymphatic drainage, MC stocking, multilayer bandaged, as well as intermittent pneumatic compression or electric calf stimulations were used. The current evidence is based on non-randomized studies, small study cohorts, as well as very heterogenous populations. The use of the intermittent pneumatic compression in CHF patients significantly increases the right auricular pressure and mean pulmonary artery pressures as well as decreases systemic vascular resistance in most patients without the clinical worsening. The transient and rapid increase in the human atrial natriuretic peptide, after an application of the MC stocking in New York Heart Association (NYHA) class II patients was observed without clinical exacerbation. An application of the multilayer bandages in NYHA classes III and IV patients lead a significant increase in the right arterial pressure and lead to transient deterioration of the right and the left ventricular functions. In the manual lymphatic drainage study, aside from expected leg circumference reduction, no clinical worsening was observed. In a pilot study performed in a small cohort of CHF patients, electrical calf stimulation use resulted in a reduction in the lean mass of the legs without cardiac function worsening. The use of local leg compression can be considered stable CHF patients without decompensated heart function for both CHF-related oedema treatment and for treatment of the concomitant diseases leading to leg swelling occurrence. The use of MC in more severe classes of CHF (NYHA III and IV) should be the subject of future clinical studies to select the safest and most efficient compression method as well as to select the patients who benefit most from this kind of treatment.
Topics: Edema; Heart Failure; Humans; Leg; Pilot Projects; Pressure
PubMed: 32710511
DOI: 10.1002/ehf2.12848 -
The Cochrane Database of Systematic... Oct 2015Pregnancy is presumed to be a major contributory factor in the increased incidence of varicose veins in women, which can in turn lead to venous insufficiency and leg... (Review)
Review
BACKGROUND
Pregnancy is presumed to be a major contributory factor in the increased incidence of varicose veins in women, which can in turn lead to venous insufficiency and leg oedema. The most common symptom of varicose veins and oedema is the substantial pain experienced, as well as night cramps, numbness, tingling, the legs may feel heavy, achy, and possibly be unsightly. Treatments for varicose veins are usually divided into three main groups: surgery, pharmacological and non-pharmacological treatments. Treatments of leg oedema comprise mostly symptom reduction rather than cure and use of pharmacological and non-pharmacological approaches.
OBJECTIVES
To assess any form of intervention used to relieve the symptoms associated with varicose veins and leg oedema in pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials of treatments for varicose veins or leg oedema, or both, in pregnancy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS
We included seven trials (involving 326 women). The trials were largely unclear for selection bias and high risk for performance and detection bias.Two studies were placebo-controlled trials. The first one compared a phlebotonic (rutoside) with placebo for the reduction in symptoms of varicose veins; the second study evaluated the efficacy of troxerutin in comparison to placebo among 30 pregnant women in their second trimester with symptomatic vulvar varicosities and venous insufficiency in their lower extremities. Data from this study were not in useable format, so were not included in the analysis. Two trials compared either compression stockings with resting in left lateral position or reflexology with rest for 15 minutes for the reduction of leg oedema. One trial compared standing water immersion for 20 minutes with sitting upright in a chair with legs elevated for 20 minutes. Women standing in water were allowed to stand or walk in place. One trial compared 20 minutes of daily foot massage for five consecutive days and usual prenatal care versus usual prenatal care. The final trial compared three treatment groups for treating leg oedema in pregnancy. The first group was assigned to lateral supine bed rest at room temperature, women in the second group were asked to sit in a bathtub of waist-deep water at 32 ± 0.5 C with their legs horizontal and the third group included the women who were randomised to sitting immersed in shoulder-deep water at 32 ± 0.5 C with legs extended downward. We did not include this study in the analysis as outcomes reported in the paper were not pre-specified outcomes of this review.We planned to use GRADE methods to assess outcomes for two different comparisons and assign a quality rating. However, only two out of three outcomes for one comparison were reported and could be assessed. Evidence from one trial (rutoside versus placebo) for the outcomes of reduction in symptoms and incidence of complications associated with varicose veins and oedema was assessed as of moderate quality. Rutoside versus placeboOne trial involving 69 women, reported that rutoside significantly reduced the symptoms associated with varicose veins (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.11 to 3.22; moderate quality evidence). The incidence of complications (deep vein thrombosis) did not differ significantly between the two groups (risk ratio (RR) 0.17, 95% CI 0.01 to 3.49; moderate quality evidence). There were no significant differences in side-effects (RR 1.30, 95% CI 0.23 to 7.28). Women's perception of pain was not reported in this trial. External pneumatic intermittent compression versus restOne trial, involving 35 women, reported no significant difference in lower leg volume when compression stockings were compared against rest (mean difference (MD) -258.80, 95% CI -566.91 to 49.31). Reflexology versus restingAnother trial, involving 55 women, compared reflexology with rest. Reflexology significantly reduced the symptoms associated with oedema (reduction in symptoms: RR 9.09, 95% CI 1.41 to 58.54). The same study showed a trend towards satisfaction and acceptability with the intervention (RR 6.00, 95% CI 0.92 to 39.11). Water immersion versus leg elevationThere was evidence from one trial, involving 32 women, to suggest that water immersion for 20 minutes in a swimming pool reduces leg volume (RR 0.43, 95% CI 0.22 to 0.83). Foot massage versus routine careOne trial, involving 80 women reported no significant difference in lower leg circumference when foot massage was compared against routine care (MD -0.11, 95% CI -1.02 to 0.80).No other primary or secondary outcomes were reported in the trials.
AUTHORS' CONCLUSIONS
There is moderate quality evidence to suggest that rutosides appear to help relieve the symptoms of varicose veins in late pregnancy. However, this finding is based on one study (69 women) and there are not enough data presented in the study to assess its safety in pregnancy. Reflexology or water immersion appears to help improve symptoms for women with leg oedema, but again this is based on two small studies (43 and 32 women, respectively).
Topics: Edema; Female; Humans; Immersion; Leg; Massage; Pregnancy; Pregnancy Complications, Cardiovascular; Pressure; Randomized Controlled Trials as Topic; Rutin; Stockings, Compression; Varicose Veins; Vasodilator Agents
PubMed: 26477632
DOI: 10.1002/14651858.CD001066.pub3 -
The Indian Journal of Medical Research Nov 2009Oedematous malnutrition, represented by its most severe form kwashiorkor, is rampant in many parts of the world and is associated with a high case fatality rate. Despite... (Review)
Review
Oedematous malnutrition, represented by its most severe form kwashiorkor, is rampant in many parts of the world and is associated with a high case fatality rate. Despite being first described more than a century ago, the pathogenesis of kwashiorkor is still not clear. The traditional thinking is that it results from a deficiency of dietary protein and is usually associated with an infection. This has now been challenged by the finding that there is no difference in diets of children developing marasmus or kwashiorkor. Nutritional oedema is associated with an increased secretion of anti-diuretic substance (probably antidiuretic hormone) which prevents the normal excretory response to water administration. Experimental studies have shown that feeding low-protein, low-calorie diets results in delayed and incomplete response to a water load, and that the livers of the animals show a reduced capacity for inactivating anti-diuretic hormone. There is now evidence that links generation of free radicals and depletion of anti-oxidants with the development of oedema in kwashiorkor.
Topics: Aldosterone; Animals; Child; Edema; Ferritins; Humans; Kwashiorkor; Malnutrition; Models, Biological; Oxidative Stress; Protein-Energy Malnutrition; Vasopressins
PubMed: 20090122
DOI: No ID Found -
Ugeskrift For Laeger Nov 2017Idiopathic oedema is a non-inflammatory interstitial oedema seen in fertile women. A hallmark is a daily increase in weight > 1.4 kg from morning until evening due to... (Review)
Review
Idiopathic oedema is a non-inflammatory interstitial oedema seen in fertile women. A hallmark is a daily increase in weight > 1.4 kg from morning until evening due to fluid retention, which shows as facial puffiness in the morning and more often abdominal increase and swollen lower extremities during the day. Patients may be disabled due to accompanying symptoms like headache, dizziness, fatigue, anxiety, and depression. The diagnosis is based on clinical features and exclusion of other causes of oedema. Non-pharmacological interventions and pharmacological therapies are reviewed.
Topics: Adult; Diagnosis, Differential; Edema; Female; Humans; Middle Aged; Weight Gain
PubMed: 29208198
DOI: No ID Found