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PubMed1993

Edematous disorders: pathophysiology of renal sodium and water retention and treatment with diuretics.

The pathogenesis of renal sodium and water retention in cardiac failure, cirrhosis, and the nephrotic syndrome may be explained by the unifying hypothesis of body fluid volume regulation. According to this hypothesis, underfilling of the arterial vascular compartment initiates a sequence of events, including activation of various neurohormonal vasoconstrictor systems, which results in enhanced renal sodium and water reabsorption, the failure to escape from the sodium-retaining effect of aldosterone, and renal resistance to atrial natriuretic peptide. In patients with low-output cardiac failure, a decrease in cardiac output results in arterial underfilling. Peripheral arterial vasodilation diminishes the fullness of the arterial vascular compartment in patients with high-output cardiac failure and cirrhosis. In the nephrotic syndrome, the decrease in plasma oncotic pressure due to hypoalbuminemia initiates arterial underfilling. The factors that are responsible for the peripheral arterial vasodilation in patients with cirrhosis remain obscure. Diuretics are initially effective in reducing the excess of total-body sodium and water in edematous patients. Loop diuretics, with or without metolazone or a thiazide diuretic, are quite useful in patients with heart failure. In cirrhosis and the nephrotic syndrome, the specific aldosterone antagonist spironolactone, alone or in combination with other diuretics, has proven to be highly efficacious. However, in all instances, the emergence of diuretic resistance represents a major limitation of diuretic therapy for the edematous patient. This diuretic resistance may be mediated by further activation of vasoconstrictor, antinatriuretic neurohormones.

Animals↗
PubMed1993

Patient knowledge about diuretic prescription.

1. In order to assess the prevalence and knowledge of diuretic prescription, 203 consecutive admissions to three general medical wards were interviewed. Additional information was collected on forms sent to general practitioners and hospital doctors responsible for each patient. 2. Prevalence of diuretic use was 31% (63 patients); other drugs only, 60% (121 patients); no drugs, 9% (19 patients). Patients gave an incorrect indication for 31% of diuretics prescribed, but for only 16% of other drugs (P < 0.005). 3. Compared with patients not taking diuretics, diuretic-users were older (mean +/- s.d., 70 years +/- 14 vs 54 +/- 20, P < 0.001), had lower abbreviated mental test scores (AMT scores seven or less, 21% vs 9%, chi 2 = 3.48, P = 0.06) and were prescribed more drugs (5.0 +/- 2.4 vs 3.2 +/- 2.0, P < 0.001). Increasing age and decreasing AMT score were associated with poorer knowledge of drug indication, but these factors could not explain fully the poor understanding of diuretic prescription. 4. Accurate recall of dose was the same for diuretics and for other agents. Knowledge about medication was not different if the general practitioner or hospital initiated treatment.

Adolescent↗
PubMed1997

Use of diuretics in chronic renal failure.

Patients with chronic renal failure retain Na+ and H2O, and they retain K- and acid. This disordered homeostasis results in hypertension, edema, hyperkalemia and acidosis. Diuretics may be used to favorably modify these disturbances. However, because of the limited filtered load of water and electrolytes, and the low renal blood flow, measures need to be taken to maximize the response to diuretics. These measures include: (a) the use of the most bioavailable drug, torasemide, when using the oral route; (b) the use of the drug with the least hepatic elimination, furosemide, when using the intravenous route; (c) the use of combinations of loop- and distal tubule-acting diuretics; (d) the use of the maximum effective diuretic dose; and (e) the use of repeated doses or constant infusion. In benefiting hypertension, vascular congestion and hyperkalemia diuretics appear to exert their effects not only on the kidneys but also on extrarenal sites, such as the vascular tree and the gastrointestinal tract. The use of diuretics, however, is not without complications, which include: intravascular volume depletion and azotemia, ototoxicity (when using loop-acting diuretics), hyperlipidemia, acute pancreatitis, hyperkalemia (when using K(+)-sparing agents), and acidosis (when using carbonic anhydrase inhibitors).

Diuretics↗
PubMed1997

[Significance of diuretics in the treatment of hypertension].

Due to new therapeutic substances the use of diuretics in the treatment of hypertension is decreasing slowly over the last few years. Nevertheless diuretics still represent one important cornerstone in the therapy of most forms of high blood pressure. Metabolic side effects of diuretics are often used as an argument against their clinical use. Indeed the diuretic therapy may lead as a function of the dosage and the duration of the therapy to an increase of total cholesterol and an impairment of the glucose tolerance. Spironolactone and other potassium sparing diuretics are "lipid-neutral". These metabolic side effects of the diuretics can be counterbalanced by the implementation of non-pharmacological means of blood pressure therapy. Body weight control seems to be of central importance. Therapy resistant forms of hypertension may be caused by many different pathogenetic mechanisms. Besides other reasons (such as secondary hypertension, non compliance ect) volume overload may represent one of the most important reasons of resistant forms of hypertension. Diuretics, especially also the aldosterone antagonists, play a central role in the control of most situations associated with volume overload in the setting of essential hypertension.

Antihypertensive Agents↗
PubMed1992

The influence of posture on the response to loop diuretics in patients with chronic cardiac failure is reduced by angiotensin converting enzyme inhibition.

The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.

Adult↗
PubMed1993

Diuretic Doppler sonography following successful repair of renal obstruction in children.

The measurement of resistive index (RI = [peak systolic velocity--end diastolic velocity]/peak systolic velocity) by Doppler sonography has demonstrated variable reliability as an indicator of pediatric urinary obstruction. By modifying Doppler studies with the addition of furosemide (diuretic Doppler sonography), we previously found significant differences between 10 nonobstructed and 10 obstructed kidneys in children (median age 7 months). The obstructed kidneys have since undergone surgical repair, and postoperative reevaluation has been performed by diuretic Doppler sonography and diuretic renography. Diuretic Doppler sonography was performed on well hydrated catheterized patients, with resistive index measurement of the renal interlobar and arcuate arteries obtained before and 10 minutes after 1 mg./kg. furosemide infusion. Following surgical repair of obstruction all 10 kidneys had stable glomerular filtration rate with improved pelvic emptying times as demonstrated by half-time. Of 6 kidneys evaluated by diuretic Doppler sonography before 3 months 2 had resistive index levels greater than 75. Of the 9 kidneys measured at 3 months or more postoperatively all had resistive index values of less than 75, even after furosemide infusion (5 kidneys underwent repeat evaluation). In our study the previously demonstrated post-diuretic elevation of resistive index in pediatric urinary obstruction was eventually reversed following surgical repair. Diuretic Doppler sonography appears to be a promising noninvasive method for evaluating pediatric hydronephrosis, providing an alternative physiological parameter with which to measure renal obstruction.

Furosemide↗
PubMed1994

The antianginal efficacy of isosorbide dinitrate therapy is maintained during diuretic treatment.

OBJECTIVES: To determine whether the use of a diuretic would maintain the antianginal efficacy of isosorbide dinitrate during 1 week of therapy. METHODS: During continuous therapy, organic nitrates have a reduction in antianginal effectiveness and cause fluid retention. The study was a randomized, double-blind, placebo-controlled crossover design examining the effect of 1 week of daily treatment with 50 mg hydrochlorothiazide/5 mg amiloride on the antianginal effectiveness of 30 mg isosorbide dinitrate administered every 6 hours. Exercise stress testing was performed before and 3 hours after administration of isosorbide dinitrate at the start and end of the placebo and diuretic treatment phases. RESULTS: The time to onset of angina (475 +/- 35 versus 490 +/- 29 seconds, difference not significant) and to moderate angina after administration of isosorbide dinitrate (542 +/- 40 versus 566 +/- 37 seconds, difference not significant) were similar at the start and end of the diuretic phase of the study but were reduced at the end of the placebo phase (471 +/- 40 versus 410 +/- 40 seconds, p < 0.05 and 531 +/- 38 versus 466 +/- 39 seconds, p < 0.05, respectively). Total exercise time and time to onset of angina 3 hours after administration of isosorbide dinitrate were longer (p < 0.005) at the end of the diuretic phase compared with the end of the placebo phase. Patients gained weight during the placebo phase and lost weight during the diuretic phase of the study. The change in weight was inversely correlated to the change in total exercise time (r = -0.53, p < 0.05). CONCLUSIONS: Patients using a diuretic with isosorbide dinitrate maintain an increased anginal threshold and total exercise time compared with placebo. Weight change is inversely related to exercise duration, and this result is consistent with fluid retention restoring cardiac preload during nitrate use. The increased anginal threshold during concurrent isosorbide dinitrate and diuretic use may be attributable to maintenance of the organic nitrate-induced reductions in cardiac preload.

Aged↗
PubMed1982

Plasma renin in long-term diuretic treatment of hypertension: effect of discontinuation and restarting therapy.

1. Plasma renin activity, body weight and blood pressure were measured before and after 7 days' treatment with bendrofluazide in ten hypertensive subjects. They were then treated with bendrofluazide alone (5 mg daily) for a minimum of 3 years. The diuretic was then discontinued and the measurements were repeated before and again after 7 days with bendrofluazide. The results were compared with those obtained before chronic treatment with the diuretic. 2. Chronic diuretic treatment was associated with a persistent and progressive rise in plasma renin activity, that fell promptly to pretreatment levels when diuretics were discontinued. This was associated with significant weight gain but no immediate significant rise in blood pressure. 3. When acutely challenged with bendrofluazide the patients showed a greater increase in plasma renin activity on the second occasion than on the first. Three out of five patients with an initially subnormal diuretic treatment. 4. Chronic diuretic treatment increased the responsiveness of the juxtaglomerular apparatus in some hypertensive patients. 5. Classification of hypertensive patients into renin subgroups may be influenced by previous therapy, even when that therapy has been discontinued for 4 weeks. In particular 'low renin hypertension' may be masked by recent use of diuretics, as shown by three of the five patients in this subgroup in the present study.

Bendroflumethiazide↗
PubMed1985

Relationship of diuretic therapy and serum magnesium levels among participants in the Multiple Risk Factor Intervention Trial.

Thiazide-like diuretics cause an increased excretion of magnesium in the urine. Low serum and selected tissue magnesium levels have been reported among diuretic users. Low magnesium levels have been associated with cardiac arrhythmias, neuromuscular changes, and increases in lipoprotein levels. The dietary intake of magnesium is borderline compared with the recommended dietary allowances. Water sources may therefore play an important role. Hard water contains more magnesium than soft water. The authors studied serum magnesium levels among special intervention Multiple Risk Factor Intervention Trial participants in two centers: Pittsburgh, Pennsylvania and Davis, California. These participants were men aged 35-57 years at entry to the trial in 1972-1974; the blood samples were obtained primarily in 1980-1981. Diuretic users primarily of chlorthalidone had an average 1 ppm lower serum magnesium level than nondiuretic users. About 15% of diuretic users had persistently lower magnesium levels on two samples approximately four months apart. The serum magnesium level was not correlated with the serum potassium level. This study is the first long-term follow-up of a well-defined group of hypertensives taking thiazide-like diuretics versus suitable controls. The results suggest that within similar populations, low serum magnesium levels are relatively rare even in the absence of supplementation with magnesium. Specific high-risk populations may exist in which a combination of diuretic therapy and low intake may contribute to magnesium deficiency. Further epidemiologic studies should include monitoring both serum and intracellular levels of magnesium among these potential high-risk groups on diuretic therapy. This approach may offer the best method of testing the relationship between water hardness, minerals, and cardiovascular disease.

Adult↗
PubMed1994

Continuous infusion of loop diuretics in the critically ill: a review of the literature.

OBJECTIVES: a) To present the pharmacodynamic concepts behind the administration of loop diuretics via continuous infusion; b) to review the clinical trials and reports in critically ill patients that have described this method of drug delivery; and c) to discuss the data. DATA SOURCES: Review of MEDLINE and International Pharmaceutical Abstracts from 1966 to the present. STUDY SELECTION: Study design was not a factor in selecting literature for this review. All studies, case reports, and case series describing infusion of a loop diuretic are included. DATA EXTRACTION: Cited literature was found in peer-reviewed clinical or basic science journals. DATA SYNTHESIS: There is a pharmacodynamic basis for the use of a controlled infusion of the loop diuretics in critically ill patients requiring extensive diuresis. Animal and human volunteer studies have demonstrated a clear improvement in efficiency of diuresis by controlled infusion Clinical studies in critically ill patients have demonstrated an improved diuretic response with a controlled infusion. Adverse effects appear to be minimal, and the amount of drug required for effect is less than the required amount for bolus administration. CONCLUSION: Administration of loop diuretics by continuous intravenous infusion may improve diuresis in critically ill patients who require prompt, controllable diuresis, or who demonstrate "diuretic tolerance" to conventional administration regimens. Despite few, well-designed studies using this method of administration in clinical practice, pharmacodynamic concepts support continuous infusion over bolus administration, including decreased dosage requirements, improved diuretic response and few adverse effects.

Animals↗
PubMed1979

Diuretics, beta-blockers or both as treatment for essential hypertension.

1 Patients with borderline (group I) and sustained hypertension (group II) were treated with beta-blocking drugs, diuretics and the combination of both. In the two groups of patients the antihypertensive effectiveness of both short-term intravenous or chronically oral propranolol was directly related to the extent to which the drug produced an absolute reduction in plasma renin activity (PRA). No such a correlation could be obtained with pindolol. In group I following beta-blockade, day-night profiles of PRA were similar to those observed in group II before treatment. Thus, in this latter subgroup, low renin profiles might reflect reduced beta-adrenergic activity. 2 When the chronically beta-blockaded patients were changed to chronic diuretic therapy it became evident that young hypertensive patients of group II showed a more pronounced BP response than the patients of group I. In those patients of group II in whom pressure was not controlled by the diuretic alone, combination with a beta-blocker led to pressure normalization. 3 The beta-blocking drug induced reduction in pressure was greater in the 25-35 yr olds, than in those older than 55. In contrast, the antihypertensive effect of the diuretic was more pronounced in the 55-70 yr olds than in those younger than 40. 4 It is concluded that sympathetic nervous system activity mainly determined PRA as well as antihypertensive effectiveness of both the beta-blockers and the diuretics. As to outpatient management it is proposed that with exception of young borderline hypertensives who seem to respond best to beta-blockers, initial antihypertensive drug therapy may consist of a diuretic agent. If the antihypertensive effect of the diuretic is insufficient, combination with a beta-blocking drug could be used to achieve the best effect.

Adrenergic beta-Antagonists↗
PubMed1982

The diuretic and natriuretic responses to stimulation of left atrial receptors in dogs with different blood volumes.

The diuretic and natriuretic responses to stimulation of atrial receptors were compared in two groups of anaesthetized dogs, one group with a high blood volume and another group with a low blood volume. A diuretic response to stimulation of the atrial receptors was obtained in the two groups of animals. Both the diuretic and the natriuretic responses to stimulation of the atrial receptors were greater in the dogs with high blood volume than in the dogs with low blood volume. In a second series of experiments, a diuretic response to stimulation of the atrial receptors was demonstrated in both groups of animals following surgical denervation of the kidney. In the denervated kidney, a large increase in heart rate, associated with stimulation of the atrial receptors, significantly contributed to the diuretic response in the dogs with high blood volume but not to the response in dogs with low blood volume. In the denervated kidney, a natriuretic response was only obtained in the dogs with high blood volume in which a large increase in heart rate was associated with stimulation of the atrial receptors. The present results show that the diuretic and natriuretic responses to stimulation of atrial receptors are greater in dogs with high blood volume than in dogs with low blood volume, and that increases in heart rate, associated with stimulation of atrial receptors, significantly contribute to the diuretic and natriuretic responses in acutely denervated kidneys in the dogs with high blood volume.

Animals↗
PubMed1997

The use of diuretics and dopamine in acute renal failure: a systematic review of the evidence.

OBJECTIVE: To evaluate the impact of diuretics and dopamine for both the prevention and treatment of renal dysfunction in the acute care setting. STUDY IDENTIFICATION AND SELECTION: Studies were identified via MEDLINE, and through bibliographies of primary and review articles. Articles were then screened by the author for studies addressing the use of diuretics or dopamine in the prevention and/or treatment of renal dysfunction. DATA ABSTRACTION AND LITERATURE APPRAISAL: From individual studies, data were abstracted regarding design features, population, intervention and outcomes. Studies were graded by levels according to their design. RESULTS: A total of 10 studies using diuretics and 30 involving dopamine were identified. Level I evidence exists against the use of diuretics for radiocontrast-induced acute tubular necrosis, and loop diuretics given after vascular surgery. There is level II evidence that diuretics do not improve outcome in patients with established acute renal failure. Level II evidence also exists against the use of dopamine in the prevention of acute tubular necrosis in multiple subsets of patients. CONCLUSIONS: Routine use of diuretics or dopamine for the prevention of acute renal failure cannot be justified on the basis of available evidence.

Journal Article↗
PubMed1978

Effects of centrally affecting drugs on the diuretic and antidiuretic actions of intracerebroventricular prostaglandin E2.

Effects of centrally affecting drugs on the diuretic and antidiuretic actions of intracerebroventricularly (i.c.v.) injected prostaglandin (PG) E2 in ethanol-anaesthetized rats were studied. PGE2, when injected i.c.v. at a dose of 1 nmole, produced diuresis followed by antidiuresis. When morphine (0.1 mM) was perfused i.c.v., urine outflow decreased and neither diuretic nor antidiuretic effects of i.c.v. PGE2 was apparent. The perfusions with picrotoxin, gamma-aminobutyric acid and L-glutamate inhibited either the diuretic or the antidiuretic effect of PGE2. On the other hand, when pentobarbital, diazepam, isoniazid and strychnine were perfused i.c.v., the diuretic action of PGE2 was diminished and antidiuresis in response to PGE2 remained unchanged. These results suggested that the diuretic and antidiuretic effects of PGE2 could be separated. The developed of the diuretic effect of PGE2 was completely blocked by amitriptyline and antidiuresis was increased. In rats pretreated i.c.v. with reserpine, the diuretic effect of PGE2 was prolonged and antidiuresis in response to PGE2 was not observed. An antidiuretic action of i.c.v. norepinephrine was not varied by reserpine. Mechanisms for both effects of PGE2 are discussed.

Amitriptyline↗
PubMed2006

Thiazide diuretics in the treatment of hypertension: an update.

Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients, the following considerations should be taken into account. Although there are some indications that chlorthalidone can offer additional advantages as compared with other compounds, a recent meta-analysis of placebo-controlled trials suggested that the beneficial effects of thiazide diuretics could be a class effect. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes, in whom thiazide diuretics should be used at the lowest active dose and possibly in combination with drugs that block the renin-angiotensin system. Finally, the current debate on whether thiazide diuretics are the first-choice drug for most patients with uncomplicated hypertension, as stated in the Seventh Joint National Committee Report, or are included in the major classes of antihypertensive agents that are suitable for initiation and maintenance of therapy, as reported in the European Society of Hypertension-European Society of Cardiology Guidelines, derives from different interpretations of controlled clinical trial data on drug class comparison and of cost-benefit analyses. However, considering that the benefit of antihypertensive drugs seems to be due principally to BP lowering per se without definitive evidence of the superiority of a particular drug class and that there is no cost-benefit analysis showing the superiority of thiazide diuretics, it is believed that these drugs should not be considered as the only first-choice drug but included among first-choice drugs.

Antihypertensive Agents↗
PubMed2006

Recent diuretic use and the risk of recurrent gout attacks: the online case-crossover gout study.

OBJECTIVE: To assess several putative risk factors, including thiazide and loop diuretics use, thought to trigger recurrent gout attacks. METHODS: We conducted an internet-based case-crossover study involving subjects who had a gout attack within the past year. Patients were recruited online and asked to provide access to medical records. Data were obtained on specific diuretic use on each day over the 2-day period prior to an acute gout attack (hazard period) and on each day of 2 days during the intercritical period (control period). We examined the relation of all diuretic use and use of specific diuretics, i.e., thiazide and loop, to the risk of recurrent gout attacks using a conditional logistic regression model adjusting for alcohol consumption and purine intake. RESULTS: One hundred ninety-seven subjects completed both control and hazard period questionnaires. Participants were predominantly male (80%) and over half had a college education. The median time between onset of gout attack and logging on to the website was 2 days. Adjusting for alcohol consumption and purine intake, the odds ratio (OR) for recurrent gout attacks from all diuretic use over the last 48 h was 3.6 (95% confidence interval 1.4-9.7). OR of recurrent gout attacks were 3.2 and 3.8 for use of thiazide and loop, respectively. CONCLUSION: Recent use of diuretics is associated with a significantly increased risk for recurrent gouty arthritis. The increased risk of gout attacks from either thiazide or possibly loop diuretic therapies represents an important modifiable risk factor in patients with gout.

Adult↗
PubMed1984

Effect of oral diuretics on pulmonary mechanics in infants with chronic bronchopulmonary dysplasia: results of a double-blind crossover sequential trial.

In a randomized double-blind crossover trial with sequential analysis, the effects of oral diuretics were compared with the effects of placebo on pulmonary mechanics in ten infants with bronchopulmonary dysplasia (BPD). Pulmonary mechanics were measured before and at the end of a week of treatment with oral diuretics (chlorothiazide, 20 mg/kg/dose and spironolactone, 1.5 mg/kg/dose) given twice daily, or placebo. Mean airway resistance decreased 35.3 cm H2O/L/s, mean specific airway conductance increased 0.095 1/L/s/cm H2O, and mean dynamic pulmonary compliance increased 1.74 mL/cm H2O during treatment with diuretics (all P less than .001), but not during treatment with placebo. The infants' rate of weight gain decreased on the first three days of diuretic treatment, but was thereafter comparable with weight gain during treatment with placebo. Fluid intake was similar in infants receiving diuretics and placebo. But, infants receiving diuretics not only had significantly increased urine output, osmolal clearance, and potassium and phosphorus excretion, but these infants also retained less fluid, and, in addition, excreted less calcium than infants receiving placebo. It is concluded that oral diuretics improve lung function in infants with chronic bronchopulmonary dysplasia; however, potassium and phosphorus depletion are potential complications of treatment.

Administration, Oral↗
PubMed2006

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: { or } and , limited to and limited to or . We searched MEDLINE (1966 - 1998), EMBASE (1974 - 1998) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006). In addition, we hand searched several abstract books of national and international American and European Societies. The search of MEDLINE and of CENTRAL was last updated in March 2006. SELECTION CRITERIA: For the purpose of this analysis, we included trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included need for ventilator support, chronic lung disease, mortality and other important clinical outcomes. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: We identified eight studies that met selection criteria. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review or the potential complications of diuretic therapy. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. AUTHORS' CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence.More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g., washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Aerosols↗