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BMJ Clinical Evidence Sep 2008Acute renal failure is characterised by abrupt and sustained decline in glomerular filtration rate, which leads to accumulation of urea and other chemicals in the blood.... (Review)
Review
INTRODUCTION
Acute renal failure is characterised by abrupt and sustained decline in glomerular filtration rate, which leads to accumulation of urea and other chemicals in the blood. The term acute kidney injury has been recently introduced to encompass a wide spectrum of acute alterations in kidney function from very mild to severe. Acute renal failure/acute kidney injury is classified according to the RIFLE criteria where a change from baseline serum creatinine or urine output determines the level of renal dysfunction.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent acute renal failure in people at high risk? What are the effects of treatments for critically ill people with acute renal failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 77 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: albumin supplementation plus loop diuretics (intravenous), aminoglycosides, aminophylline, amphotericin B, calcium channel blockers, contrast media, dialysis membranes, dopamine, fenoldopam, loop diuretics, mannitol, N-acetylcysteine, natriuretic peptides, renal replacement therapy, sodium bicarbonate-based fluids, sodium chloride-based fluids, and theophylline.
Topics: Acetylcysteine; Acute Kidney Injury; Fenoldopam; Humans; Renal Dialysis; Renal Insufficiency; Renal Replacement Therapy
PubMed: 19445797
DOI: No ID Found -
Respirology (Carlton, Vic.) Aug 2017Inhaled mucoactive agents are used in respiratory disease to improve mucus properties and enhance secretion clearance. The effect of mannitol, recombinant human... (Meta-Analysis)
Meta-Analysis Review
Inhaled mucoactive agents are used in respiratory disease to improve mucus properties and enhance secretion clearance. The effect of mannitol, recombinant human deoxyribonuclease/dornase alfa (rhDNase) and hypertonic saline (HS) or normal saline (NS) are not well described in chronic lung conditions other than cystic fibrosis (CF). The aim of this review was to determine the benefit and safety of inhaled mucoactive agents outside of CF. We searched Medline, Embase, CINAHL and CENTRAL for randomized controlled trials investigating the effects of mucoactive agents on lung function, adverse events (AEs), health-related quality of life (HRQOL), hospitalization, length of stay, exacerbations, sputum clearance and inflammation. There were detrimental effects of rhDNase in bronchiectasis, with average declines of 1.9-4.3% in forced expiratory volume in 1 s (FEV ) and 3.7-5.4% in forced vital capacity (FVC) (n = 410, two studies), and increased exacerbation risk (relative risk = 1.35, 95% CI = 1.01-1.79 n = 349, one study). Some participants exhibited a reduction in FEV (≥10-15%) with mucoactive agents on screening (mannitol = 158 of 1051 participants, rhDNase = 2 of 30, HS = 3 of 80). Most AEs were mild and transient, including bronchospasm, cough and breathlessness. NS eased symptomatic burden in COPD, while NS and HS improved spirometry, HRQOL and sputum burden in non-CF bronchiectasis. Mannitol improved mucociliary clearance in asthma and bronchiectasis, while the effects of N-acetylcysteine were unclear. In chronic lung diseases outside CF, there are small benefits of mannitol, NS and HS. Adverse effects of rhDNase suggest this should not be administered in non-CF bronchiectasis.
Topics: Acetylcysteine; Administration, Inhalation; Bronchiectasis; Chronic Disease; Deoxyribonuclease I; Expectorants; Forced Expiratory Volume; Humans; Lung Diseases; Mannitol; Mesna; Mucociliary Clearance; Quality of Life; Recombinant Proteins; Saline Solution, Hypertonic; Symptom Flare Up; Vital Capacity
PubMed: 28397992
DOI: 10.1111/resp.13047 -
Swiss Medical Weekly Aug 2019Asthma is associated with bronchial hyperresponsiveness, assessed by bronchial provocation tests such as the mannitol test. We aimed to assess the data on sensitivity...
OBJECTIVE
Asthma is associated with bronchial hyperresponsiveness, assessed by bronchial provocation tests such as the mannitol test. We aimed to assess the data on sensitivity and specificity of the mannitol test in diagnosing asthma.
DATA SOURCES
We searched electronically the Medline, Embase and Central databases from 1997 to 2019.
STUDY SELECTION
Inclusion criteria were the assessment of the validity of the mannitol test. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Data were extracted according to a prespecified list and analysed qualitatively.
RESULTS
A total of 27 studies (4589 individuals, age 6–85 years, cross-sectional [n = 18] and case-controlled [n = 9] study design) were included. Overall sensitivity and specificity ranged from 8% (95% confidence interval [CI] 1–27) to 100% (95% CI 93–100) and 75% (95% CI 67–82) to 100% (95% CI 85–100). Excluding case-controlled design, studies conducted in a clinical setting showed a range from 19% (95% CI 14–27) to 91% (95% CI 59–100) for sensitivity and from 75% (95% CI 67–82) to 100% (95% CI 80–100) for specificity. Heterogeneity was high owing to differences in the populations examined and the methods used.
CONCLUSIONS
Studies on the accuracy of the mannitol test were heterogeneous. Overall specificity was higher than sensitivity and therefore the mannitol test seems to be a suitable diagnostic tool to confirm asthma. However, the high level of heterogeneity among the included studies makes a conclusive statement on the accuracy of the mannitol test difficult and further research is needed. As bronchial provocation tests can be especially useful in patients with an intermediate probability of asthma diagnosis, further studies are needed that include subjects with asthma symptoms but intermediate probability of asthma diagnosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchial Provocation Tests; Child; Diagnostic Tests, Routine; Female; Humans; Male; Mannitol; Middle Aged; Sensitivity and Specificity; Young Adult
PubMed: 31476241
DOI: 10.4414/smw.2019.20100 -
Critical Care Medicine May 2013Intracranial hypertension and cerebral edema are known contributors to secondary brain injury and to poor neurologic outcomes. Small volume solutions of exceedingly high... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND AND PURPOSE
Intracranial hypertension and cerebral edema are known contributors to secondary brain injury and to poor neurologic outcomes. Small volume solutions of exceedingly high osmolarity, such as 23.4% saline, have been used for the management of intracranial hypertension crises and as a measure to prevent or reverse acute brain tissue shifts. We conducted a systematic literature review on the use of 23.4% saline in neurocritically ill patients and a meta-analysis of the effect of 23.4% saline on intracranial pressure reduction.
DESIGN
We searched computerized databases, reference lists, and personal files to identify all clinical studies in which 23.4% saline has been used for the treatment of neurocritical care patients. Studies that did not directly involve either effects on cerebral hemodynamics or the treatment of patients with clinical or radiographic evidence of intracranial hypertension and/or cerebral swelling were eliminated.
MEASUREMENTS AND MAIN RESULTS
We identified 11 clinical studies meeting eligibility criteria. A meta-analysis was performed to evaluate the percent decrease in intracranial pressure and the 95% confidence intervals, from baseline to 60 minutes or nadir from the six studies from which this information could be extracted. A fixed effects meta-analysis estimated that the percent decrease in intracranial pressure from baseline to either 60 minutes or nadir after administration of 23.4% saline was 55.6% (se 5.90; 95% confidence interval, 43.99-67.12; p < 0.0001).
CONCLUSIONS
Highly concentrated hypertonic saline such as 23.4% provides a small volume solution with low cost and an over 50% reduction effect on raised intracranial pressure. Side effects reported are minor overall in view of the potentially catastrophic event that is being treated. High quality data are still needed to define the most appropriate osmotherapeutic agent, the optimal dose, the safest and most effective mode of administration and to further elucidate the mechanism of action of 23.4% saline and of osmotherapy in general.
Topics: Brain Edema; Brain Injuries; Critical Care; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Intracranial Hypertension; Intracranial Pressure; Male; Mannitol; Risk Assessment; Saline Solution, Hypertonic; Survival Rate; Treatment Outcome
PubMed: 23591212
DOI: 10.1097/CCM.0b013e31827ca4b3 -
Journal of Neurosurgical Anesthesiology Jul 2019Despite clinical use spanning 50+ years, questions remain concerning the optimal use of mannitol. The published reviews with meta-analysis frequently focused on... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Despite clinical use spanning 50+ years, questions remain concerning the optimal use of mannitol. The published reviews with meta-analysis frequently focused on mannitol's effects on a specific physiological aspect such as intracranial pressure (ICP) in sometimes heterogeneous patient populations. A comprehensive review of mannitol's effects, as well as side effects, is needed.
METHODS
The databases Medline (OvidSP), Embase (OvidSP), and NLM PubMed were systematically searched for randomized controlled trials (RCTs) comparing mannitol to a control therapy in either the critical care or perioperative setting. Meta-analysis was performed when feasible to examine mannitol's effects on outcomes, including ICP, cerebral perfusion pressure, mean arterial pressure (MAP), brain relaxation, fluid intake, urine output, and serum sodium. Systematic literature search was also performed to understand mannitol-related complications.
RESULTS
In total 55 RCTs were identified and 7 meta-analyses were performed. In traumatic brain injury, mannitol did not lead to significantly different MAP (SMD [95% confidence interval (CI)] =-3.3 [-7.9, 1.3] mm Hg; P=0.16) but caused significantly different serum sodium concentrations (SMD [95% CI]=-8.0 [-11.0, -4.9] mmol/L; P<0.00001) compared with hypertonic saline. In elective craniotomy, mannitol was less likely to lead to satisfactory brain relaxation (RR [95% CI]=0.89 [0.81, 0.98]; P=0.02), but was associated with increased fluid intake (SMD [95% CI]=0.67 [0.21, 1.13] L; P=0.004), increased urine output (SMD [95% CI]=485 [211, 759] mL; P=0.0005), decreased serum sodium concentration (SMD [95% CI]=-6.2 [-9.6, -2.9] mmol/L; P=0.0002), and a slightly higher MAP (SMD [95% CI]=3.3 [0.08, 6.5] mm Hg; P=0.04) compared with hypertonic saline. Mannitol could lead to complications in different organ systems, most often including hyponatremia, hyperkalemia, and acute kidney injury. These complications appeared dose dependent and had no long-term consequences.
CONCLUSIONS
Mannitol is effective in accomplishing short-term clinical goals, although hypertonic saline is associated with improved brain relaxation during craniotomy. Mannitol has a favorable safety profile although it can cause electrolyte abnormality and renal impairment. More research is needed to determine its impacts on long-term outcomes.
Topics: Critical Care; Diuretics, Osmotic; Humans; Mannitol; Neurosurgery; Neurosurgical Procedures; Randomized Controlled Trials as Topic
PubMed: 29952815
DOI: 10.1097/ANA.0000000000000520 -
Medeniyet Medical Journal Jun 2022Management of increased intracranial pressure in traumatic brain injury remains challenging in neurosurgical emergencies. The mainstay of medical management for...
Management of increased intracranial pressure in traumatic brain injury remains challenging in neurosurgical emergencies. The mainstay of medical management for increased intracranial pressure is hyperosmolar therapy with mannitol or hypertonic saline. Mannitol has been the "gold standard" osmotic agent for almost a century. Given its wide usage, there has been a dilemma of concern because of its adverse effects. Over the past few decades, hypertonic saline has become an increasingly better alternative. To date, there is no consensus on the optimal therapeutic dose and concentration of hypertonic saline for treating increased intracranial pressure. This systematic review aimed to compare the efficacy of hypertonic saline and mannitol in the management of traumatic brain injury and investigate the optimal dose and concentration of hypertonic saline for the treatment. Extensive research was conducted on PubMed, DOAJ, and Cochrane databases. Studies published within the last 20 years were included. Research articles in the form of meta-analyses, clinical trials, and randomized controlled trials were preferred. Those with ambiguous remarks, irrelevant correlations to the main issue, or a focus on other disorders were excluded. Nineteen studies were included in the systematic review. Eleven studies have stated that hypertonic saline and mannitol were equally efficacious, whereas eight studies have reported that hypertonic saline was superior. Moreover, 3% hypertonic saline was the main concentration most discussed in research. Improvements in increased intracranial pressure, cerebral perfusion pressure, survival rate, brain relaxation, and systemic hemodynamics were observed. Hypertonic saline is worthy of consideration as an excellent alternative to mannitol. This study suggests 3% hypertonic saline as the optimal concentration, with the therapeutic dose from 1.4 to 2.5 mL/kg, given as a bolus.
PubMed: 35735001
DOI: 10.4274/MMJ.galenos.2022.75725 -
The Cochrane Database of Systematic... Jul 2007Mannitol is an osmotic agent and a free radical scavenger which might decrease oedema and tissue damage in stroke. (Review)
Review
BACKGROUND
Mannitol is an osmotic agent and a free radical scavenger which might decrease oedema and tissue damage in stroke.
OBJECTIVES
To test whether treatment with mannitol reduces short and long-term case fatality and dependency after acute ischaemic stroke or intracerebral haemorrhage (ICH).
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (searched December 2006), MEDLINE (1966 to January 2007), the Chinese Stroke Trials Register (searched November 2006), the China Biological Medicine Database (searched December 2006) and the Latin-American database LILACS (1982 to December 2006). We also searched the database of Masters and PhD degree theses at Sao Paulo University (searched January 2007), and neurology and neurosurgery conference proceedings in Brazil from 1965 to 2006. In an effort to identify further published, ongoing and unpublished studies we searched reference lists and contacted authors of published trials.
SELECTION CRITERIA
We included randomised controlled trials comparing mannitol with placebo or open control in patients with acute ischaemic stroke or non-traumatic intracerebral haemorrhage.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed quality, extracted data, and performed the data analysis.
MAIN RESULTS
Three small trials, involving 226 participants, were included. One trial included patients with presumed ischaemic stroke without computerised tomography (CT) verification, and the other two trials included patients with CT-verified ICH. Data on the primary outcome measure (death and dependency) were not available in any of the trials. Death and disability could be calculated in the larger ICH trial without differences between the mannitol and control groups. Case fatality was not reported in the trial of ischaemic stroke. Case fatality did not differ between the mannitol and control groups in the ICH trials. Adverse events were either not found or not reported. The change in clinical condition was reported in two trials, and the proportion of those with worsening or not improving condition did not differ significantly between mannitol-treated patients and controls. Based on these three trials neither beneficial nor harmful effects of mannitol could be proved. Although no statistically significant differences were found between the mannitol-treated and control groups, the confidence intervals for the treatment effect estimates were wide and included both clinically significant benefits and clinically significant harms as possibilities.
AUTHORS' CONCLUSIONS
There is currently not enough evidence to support the routine use of mannitol in acute stroke patients. Further trials are needed to confirm or refute whether mannitol is beneficial in acute stroke.
Topics: Acute Disease; Brain Edema; Brain Ischemia; Cerebral Hemorrhage; Diuretics, Osmotic; Humans; Mannitol; Randomized Controlled Trials as Topic
PubMed: 17636655
DOI: 10.1002/14651858.CD001153.pub2 -
The Cochrane Database of Systematic... Sep 2018Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review.
OBJECTIVES
To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 23 April 2018.Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 07 June 2018.
SELECTION CRITERIA
All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance.
DATA COLLECTION AND ANALYSIS
Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence.
MAIN RESULTS
The searches identified 69 trials, of which 19 (2565 participants) met our inclusion criteria. Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Dornase alfa compared to placebo or no treatmentDornase alfa improved forced expiratory volume at one second at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed no difference between groups for changes in quality of life. There was a decrease in pulmonary exacerbations with dornase alfa in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.Dornase alfa: daily versus alternate dayOne cross-over trial (43 children) found no differences between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence).Dornase alfa compared to other medications that improve airway clearanceResults for these comparisons were mixed. One trial (43 children) showed a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found a difference in quality of life favouring dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence).When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash.
AUTHORS' CONCLUSIONS
There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.
Topics: Adolescent; Child; Child, Preschool; Cystic Fibrosis; Deoxyribonuclease I; Expectorants; Forced Expiratory Volume; Humans; Infant; Mannitol; Randomized Controlled Trials as Topic; Recombinant Proteins; Saline Solution, Hypertonic; Vital Capacity
PubMed: 30187450
DOI: 10.1002/14651858.CD001127.pub4 -
Annals of Allergy, Asthma & Immunology... Sep 2011Exercise challenge testing is the typical method for diagnosing exercise induced bronchoconstriction; however, alternate tests have been developed. (Review)
Review
BACKGROUND
Exercise challenge testing is the typical method for diagnosing exercise induced bronchoconstriction; however, alternate tests have been developed.
OBJECTIVE
The purpose of this paper was to summarize the current literature comparing eucapnic voluntary hyperpnea and mannitol with standard exercise challenge testing to determine whether either test is a suitable alternative to standard exercise testing for the diagnosis of exercise-induced bronchoconstriction.
METHODS
Using valid systematic review methods, a comprehensive search strategy to avoid publication bias, we identified 10 studies that compared exercise challenge testing with either eucapnic voluntary hyperpnea or mannitol.
RESULTS
For the 7 diagnostic cross-sectional studies that examined eucapnic voluntary hyperpnea, the sensitivity and specificity values were heterogeneous, ranging from 25 to 90% for sensitivity and 0 to 71% for specificity. In the 3 diagnostic cross-sectional studies that evaluated mannitol, the sensitivity and specificity ranged from 58 to 96% and 65 to 78%, respectively. For most studies, a representative spectrum of participants being tested was not used.
CONCLUSION
Given the heterogeneity in sensitivity and specificity of eucapnic voluntary hyperpnea studies and the relatively small number of studies that have examined mannitol, insufficient evidence is available to conclude that either of these tests are suitable alternatives to exercise challenge testing to detect exercise-induced bronchoconstriction. Additional research is required.
Topics: Asthma, Exercise-Induced; Bronchial Provocation Tests; Exercise Test; Female; Humans; Male; Mannitol; Sensitivity and Specificity
PubMed: 21875541
DOI: 10.1016/j.anai.2011.06.013 -
The Cochrane Database of Systematic... Feb 2018Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review.
OBJECTIVES
To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 28 September 2017.
SELECTION CRITERIA
All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
Six studies (reported in 50 publications) were included with a total of 784 participants.Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population.Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole.While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies.Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality.For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to very low quality and should be interpreted with caution. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects in both treatment groups. Where rates of adverse events could be compared, statistically no significant differences were found between mannitol and control groups; although some of these events may have clinical relevance for people with CF.For the comparisons of mannitol to dornase alfa alone and to mannitol plus dornase alfa, very low-quality evidence from a 12-week cross-over study of 28 participants showed no statistically significant differences in the recorded domains of health-related quality of life or measures of lung function. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations.In terms of secondary outcomes of the review (pulmonary exacerbations, hospitalisations, symptoms, sputum microbiology), evidence provided by the included studies was more limited. For all comparisons, no consistent statistically significant and clinically meaningful differences were observed between mannitol and control treatments (including dornase alfa).
AUTHORS' CONCLUSIONS
There is moderate-quality evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is low to very low-quality evidence suggesting no difference in quality of life for participants taking mannitol compared to control. This review provides very low-quality evidence suggesting no difference in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa.The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term. Furthermore, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice.
Topics: Administration, Inhalation; Adult; Child; Cystic Fibrosis; Deoxyribonuclease I; Humans; Mannitol; Mucociliary Clearance; Powders; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Function Tests
PubMed: 29424930
DOI: 10.1002/14651858.CD008649.pub3