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PloS One 2017Perioperative infusion of adenosine has been suggested to reduce the requirement for inhalation anesthetics, without causing serious adverse effects in humans. We... (Meta-Analysis)
Meta-Analysis
PURPOSE
Perioperative infusion of adenosine has been suggested to reduce the requirement for inhalation anesthetics, without causing serious adverse effects in humans. We conducted a meta-analysis of randomized controlled trials evaluating the effect of adenosine on postoperative analgesia.
METHODS
We retrieved articles in computerized searches of Scopus, Web of Science, PubMed, EMBASE, and Cochrane Library databases, up to July 2016. We used adenosine, postoperative analgesia, and postoperative pain(s) as key words, with humans, RCT, and CCT as filters. Data of eligible studies were extracted, which included pain scores, cumulative opioid consumption, adverse reactions, and vital signs. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed-effects or random-effects models, depending on the heterogeneity of the included trials.
RESULTS
In total, 757 patients from 9 studies were included. The overall effect of adenosine on postoperative VAS/VRS scores and postoperative opioid consumption was not significantly different from that of controls (P >0.1). The occurrence of PONV and pruritus was not statistically significantly different between an adenosine and nonremifentanil subgroup (P >0.1), but the rate of PONV occurrence was greater in the remifentanil subgroup (P <0.01). Time to first postoperative analgesic requirement in the adenosine group was not significantly difference from that of the saline group (SMD = 0.07, 95%CI: -0.28 to 0.41, P = 0.71); but this occurred significantly later than with remifentanil (SMD = 1.10, 95%CI: 2.48 to 4.06, P < 0.01). Time to hospital discharge was not significantly different between the control and adenosine groups (P = 0.78). The perioperative systolic blood pressure was significantly lower in the adenosine than in the control group in the mannitol subgroup (P < 0.01). The incidence of bradycardia, transient first- degree atrioventricular block, and tachycardia was not significantly different between the adenosine and control groups (P > 0.1).
CONCLUSION
Adenosine has no analgesic effect or prophylactic effect against PONV, but reduce systolic blood pressure and heart rates. Adenosine may benefit patients with hypertension, ischemic heart disease, and tachyarrhythmia, thereby improving cardiac function.
Topics: Adenosine; Adolescent; Adult; Aged; Analgesia; Analgesics, Opioid; Female; Humans; Male; Middle Aged; Pain, Postoperative; Young Adult
PubMed: 28333936
DOI: 10.1371/journal.pone.0173518 -
Clinics (Sao Paulo, Brazil) Nov 2014Staphylococcus aureus is an important cause of infections and HIV-infected individuals are frequently susceptible to this pathogen. The aim of this study was to perform... (Review)
Review
Methicillin-resistant Staphylococcus aureus in HIV patients: risk factors associated with colonization and/or infection and methods for characterization of isolates - a systematic review.
Staphylococcus aureus is an important cause of infections and HIV-infected individuals are frequently susceptible to this pathogen. The aim of this study was to perform a systematic review to identify both the risk factors associated with colonization/infection by methicillin-resistant S. aureus in HIV patients and the methods used for characterization of isolates. An electronic search of articles published between January 2001 and December 2013 was first conducted. Among 116 studies categorized as being at a quality level of A, B or C, only 9 studies were considered to have high methodological quality (level A). The majority of these studies were retrospective (4/9 studies). The risk factors associated with colonization/infection by S. aureus were use of antimicrobials (4/9 studies), previous hospitalization (4/9 studies) and low CD4+ T lymphocyte counts (<200 cells/μl) (3/9 studies). Culture in mannitol salt agar (3/9 studies) and the latex agglutination test (5/9 studies) were the main methods used for bacterial phenotypic identification. Genotypic profiles were accessed by pulsed-field gel electrophoresis (6/9 studies) and USA300 was the most prevalent lineage (5/9 studies). Most isolates were resistant to erythromycin (3/9 studies) and susceptible to vancomycin (4/9 studies). Ultimately, use of antimicrobials and previous hospitalization were the main risk factors for colonization/infection by methicillin-resistant S. aureus in HIV-infected individuals. However, the numbers of evaluated patients, the exclusion and inclusion criteria and the characterization of the S. aureus isolates were not uniform, which made it difficult to establish the characteristics associated with HIV patients who are colonized/infected by S. aureus.
Topics: Anti-Bacterial Agents; HIV Infections; Humans; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Risk Factors; Staphylococcal Infections
PubMed: 25518036
DOI: 10.6061/clinics/2014(11)11 -
Surgical Neurology International 2024This study strives to provide a current and thorough assessment of the comparative efficacy and safety between equiosmolar quantities of hypertonic saline (HS) and...
BACKGROUND
This study strives to provide a current and thorough assessment of the comparative efficacy and safety between equiosmolar quantities of hypertonic saline (HS) and mannitol in facilitating brain relaxation for patients undergoing elective craniotomies.
METHODS
This systematic review and meta-analysis, following preferred reporting items for systematic reviews and meta-analyses guidelines, compared the efficacy and safety of equiosmolar concentrations of mannitol and HS in elective craniotomies. PubMed, Scopus, Cochrane Library, ScienceDirect, and Proquest databases were searched using keywords related to mannitol, HS, and craniotomy. Results were analyzed through a random-effects model using Mantel-Haenszel risk ratio and standard mean difference. < 0.05 was considered significant.
RESULTS
Thirteen randomized controlled trials encompassing 965 patients (516 in the HS group and 448 in the mannitol group) were analyzed. The quality of studies was moderate-to-high, and no significant publication bias was observed. The primary outcome, brain relaxation, favored HS over mannitol without significant heterogeneity. Mannitol was associated with increased urine output compared to HS, irrespective of dose, with high heterogeneity. HS was linked to significantly reduced fluid input, confirmed by subgroup analysis with lower heterogeneity. No significant difference was found in serum osmolality between the two agents. Serum sodium (Na) levels favored HS, whereas arterial blood Na levels also favored HS despite considerable heterogeneity. Maximum mean arterial pressure was higher with HS, but it displayed significant heterogeneity. Maximum central venous pressure showed no significant difference between the two agents, with moderate heterogeneity.
CONCLUSION
HS appears more effective than mannitol in achieving brain relaxation, and it may offer advantages in fluid management and Na balance. Clinicians should consider these findings when selecting hyperosmotic agents for neurosurgical procedures. Further research is needed to address heterogeneity in certain outcomes and guide clinical practice.
PubMed: 38741989
DOI: 10.25259/SNI_994_2023 -
Advances in Nutrition (Bethesda, Md.) Dec 2022Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of... (Meta-Analysis)
Meta-Analysis
Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.
Topics: Adult; Child; Humans; Infant; Child, Preschool; Zinc; Nutritional Status
PubMed: 36055780
DOI: 10.1093/advances/nmac088 -
Annals of Vascular Surgery Jul 2021To assess the effect of various preventative interventions for reducing the incidence of postoperative acute kidney injury (AKI) in patients undergoing elective... (Meta-Analysis)
Meta-Analysis
BACKGOUND
To assess the effect of various preventative interventions for reducing the incidence of postoperative acute kidney injury (AKI) in patients undergoing elective abdominal aortic aneurysm (AAA) repair.
METHODS
We included randomized controlled trials of 10 patients or more which tested a preventative intervention versus standard therapy or placebo in patients undergoing elective AAA repair using the open or endovascular approach. Studies including mixed patient populations such as those with aortic occlusive disease, thoracoabdominal aneurysms or ruptured aneurysms were ineligible for review. We searched Medline (1966-2019), EMBASE (1947-2019), CINAHL (1961-2019), Web of Science (1945-2019), Scopus (1966-2019), and The Cochrane Library (1996-2019) for trials available as published manuscripts in English. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Where possible we pooled the results of similar interventions using random effects meta-analysis.
RESULTS
We included 17 trials involving 1443 participants. Most trials were small, single-center studies, with varying definitions of AKI and a high or moderate risk of bias. The preventative strategies with possible protective effects were mannitol, a composite of antioxidant supplements, an open extraperitoneal approach, and human atrial natriuretic peptide (hANP). Curcumin, methylprednisolone, carbon dioxide contrast medium, hemodynamic monitoring and N-acetylcysteine were found to be ineffective. Six trials with a total of 355 participants reported on remote ischemic preconditioning (RIPC) and our meta-analysis showed no statistically significant difference between RIPC and standard treatment (OR 1.20, 95% CI 0.37, 3.89); although the results should be interpreted with caution due to considerable statistical heterogeneity (I = 70%). None of the interventions studied significantly reduced receipt of renal replacement therapy (RRT).
CONCLUSIONS
Interventions that have shown some potential to reduce AKI after AAA repair include mannitol, a composite of antioxidant supplements, an open extraperitoneal approach and hANP. These conclusions are limited by the small size, high risk of bias and inconsistency of the included trials. Large, high quality, multi-center randomized trials will help determine which interventions are effective in reducing the incidence of postoperative AKI among patients undergoing elective AAA repair.
Topics: Acute Kidney Injury; Antioxidants; Aortic Aneurysm, Abdominal; Curcumin; Elective Surgical Procedures; Endovascular Procedures; Humans; Ischemic Preconditioning; Postoperative Complications; Preoperative Care; Vascular Surgical Procedures
PubMed: 33548402
DOI: 10.1016/j.avsg.2020.12.061 -
Journal of Cardiothoracic Surgery May 2022Surgical procedures in the heart requires protection of the heart from ischemia-reperfusion injury. Cardioplegia is the primary myocardial protective method in use.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical procedures in the heart requires protection of the heart from ischemia-reperfusion injury. Cardioplegia is the primary myocardial protective method in use. Histidine-tryptophan-ketoglutarate (HTK) solution is an intracellular cardioplegic solution that was initially used to preserve organs for transplantation.
METHODS
A systematic electronic search was conducted in July 2021, in four databases; PubMed, Scopus, Web of Science, and Cochrane Library for eligible randomized controlled trials. The results were screened and the eligible trials were identified. Thereafter, the relevant data were extracted and pooled as mean difference or risk ratio, and 95% confidence interval in an inverse variance method using RevMan software.
RESULTS
This review included 12 trials (n = 1327). HTK solution has resulted significantly in shorter intensive care unit stay (MD = - 0.09; 95% CI [- 0.15, - 0.03], p = 0.006), and shorter hospital stay (MD = - 0.51; 95% CI [- 0.71, - 0.31], p < 0.00001). Moreover, the patients who received the HTK solution had significantly lower levels of creatine kinase (after 4-7 h (MD = - 157.52; 95% CI [- 272.31, - 42.19], p = 0.007), and 24 h (MD = - 136.62; 95% CI [- 267.20, - 6.05], p = 0.04)), as well as creatine kinase muscle brain band (after 44-48 h (MD = - 3.35; 95% CI [- 5.69, - 1.02], p = 0.005)).
CONCLUSION
HTK solution had the same efficacy and safety as other cardioplegic solutions in most of the clinical parameters. Furthermore, the solution showed superiority in fastening the recovery and protecting the myocardium at the biochemical level. HTK solution provides longer myocardial protection; therefore, it limits surgical interruption. HTK solution can be used as an alternative to the currently used cardioplegic solutions.
Topics: Cardioplegic Solutions; Creatine Kinase; Glucose; Heart Arrest, Induced; Humans; Mannitol; Myocardium; Potassium Chloride; Procaine
PubMed: 35642063
DOI: 10.1186/s13019-022-01891-x -
The Cochrane Database of Systematic... May 2014Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic response. This fails to eliminate the bacteria, and the large concentration of host-derived protease may contribute to the airway damage. The sensation of retained mucus is itself a cause of suffering, and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients.Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions, probably by inducing a liquid flux into the airway surface, which alters mucus rheology in a way favourable to mucociliary clearance. Inhaled dry powder mannitol has a similar effect. Such agents are an attractive approach to the problem of mucostasis, and deserve further clinical evaluation.
OBJECTIVES
To determine whether inhaled hyperosmolar substances are effective in the treatment of bronchiectasis.
SEARCH METHODS
We searched the Cochrane Airways Group Specialised Register, trials registries, and the reference lists of included studies and review articles. Searches are current up to April 2014.
SELECTION CRITERIA
Any randomised controlled trial (RCT) using hyperosmolar inhalation in patients with bronchiectasis not caused by cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors assessed studies for suitability. We used standard methods recommended by The Cochrane Collaboration.
MAIN RESULTS
Eleven studies met the inclusion criteria of the review (1021 participants).Five studies on 833 participants compared inhaled mannitol with placebo but poor outcome reporting meant we could pool very little data and most outcomes were reported by only one study. One 12-month trial on 461 participants provided results for exacerbations and demonstrated an advantage for mannitol in terms of time to first exacerbation (median time to exacerbation 165 versus 124 days for mannitol and placebo respectively (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63 to 0.96, P = 0.022) and number of days on antibiotics for bronchiectasis exacerbations was significantly better with mannitol (risk ratio (RR) 0.76, 95%CI 0.58 to 1.00, P = 0.0496). However, exacerbation rate per year was not significantly different between mannitol and placebo (RR 0.92 95% CI 0.78 to 1.08). The quality of this evidence was rated as moderate. There was also an indication, from only three trials, again based on moderate quality evidence, that mannitol improves health-related quality of life (mean difference (MD) -2.05; 95% CI -3.69 to -0.40). An analysis of adverse events data, also based on moderate quality evidence, revealed no difference between mannitol and placebo (OR 0.96; 95% CI 0.61 to 1.51). Two additional small trials on 25 participants compared mannitol versus no treatment and the data from these studies were inconclusive.Four studies (combined N = 113) compared hypertonic saline versus isotonic saline. On most outcomes there were conflicting results and the opportunities for the statistical aggregation of data from studies was very limited. It is not possible to draw robust conclusions for this comparison and judgments should be reserved until further data are available.
AUTHORS' CONCLUSIONS
There is an indication from a single, large, unpublished study that inhaled mannitol increases time to first exacerbation in patients with bronchiectasis. In patients with near normal lung function, spirometry does not change dramatically with mannitol and adverse events are not more frequent than placebo. Further investigation is required in a patient population with impaired lung function.It is not possible to draw firm conclusions regarding the effect of nebulised hypertonic saline due to significant differences in the methodology, patient groups, and findings amongst the limited data available. The data suggest that it is unlikely to have benefit over isotonic saline in patients with milder disease, and hence future studies should test its use in those with more severe disease.
Topics: Anti-Bacterial Agents; Bronchiectasis; Cross-Over Studies; Health Status; Humans; Hypertonic Solutions; Mannitol; Mucociliary Clearance; Osmolar Concentration; Powders; Randomized Controlled Trials as Topic
PubMed: 24817558
DOI: 10.1002/14651858.CD002996.pub3 -
Artificial Organs May 2016Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the... (Meta-Analysis)
Meta-Analysis Review
Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the evidence comparing preservation solutions for heart preservation. Studies were searched in PubMed, Embase, the Cochrane Library, the Transplant Library, and the International Clinical Trials Registry Platform. The primary outcomes were patient survival and donor heart dysfunction. The secondary outcomes were in-hospital mortality and enzyme gene expression. The University of Wisconsin solution (UW) was associated with a significantly improved survival at 30 days and 90 days (hazard ratio = 1.16, 95% confidence interval [CI] = 1.11-1.22, P < 0.00001; risk difference [RD] = 0.03, 95% CI = 0.01-0.05, P = 0.002), compared with Celsior. Hearts preserved with UW exhibited less ischemic necrosis than those preserved with Celsior (RD = -0.07, 95% CI = -0.08 to 0.05, P < 0.00001). UW was associated with better survival compared with histidine-tryptophan-ketoglutarate solution (HTK). There was no statistical difference in donor heart dysfunction and in-hospital mortality outcomes when comparing HTK with Celsior solution. During static cold storage preservation, this study suggests that UW solution has better clinical outcomes for heart transplantation compared with the other two organ preservation solutions. Besides, the protective effect of Celsior solution is similar to HTK solution in donor heart preservation.
Topics: Adenosine; Allografts; Allopurinol; Disaccharides; Electrolytes; Glucose; Glutamates; Glutathione; Heart; Heart Transplantation; Histidine; Humans; Insulin; Mannitol; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Procaine; Raffinose
PubMed: 26526678
DOI: 10.1111/aor.12585 -
The Cochrane Database of Systematic... May 2020Several 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
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: 12 December 2019.
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 36 unique 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; Forced Expiratory Volume; Humans; Mannitol; Mucociliary Clearance; Powders; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Function Tests; Vital Capacity
PubMed: 32358807
DOI: 10.1002/14651858.CD008649.pub4 -
The Cochrane Database of Systematic... Apr 2016Dornase 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: 30 November 2015.Clinicaltrials.gov was also searched to identify unpublished or ongoing trials. Date of most recent search: 28 November 2015.
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.
MAIN RESULTS
The searches identified 54 trials, of which 19 (including a total of 2565 participants) met our inclusion criteria. Three additional papers examined the healthcare cost from one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no dornase alfa treatment (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa with 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.Compared to placebo, forced expiratory volume at one second improved in the intervention groups, with significant differences at one, three, six months and two years. There was also a significant improvement in lung clearance index at one month. There was a decrease in pulmonary exacerbations compared to placebo in trials of longer duration. The quality of the evidence from placebo-controlled trials was moderate to high for outcomes of lung function and pulmonary exacerbations. Limited, low quality evidence was available for changes in quality of life from baseline. 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.The results for trials comparing dornase alfa to other medications that improve airway clearance (hypertonic saline or mannitol) were mixed, with one trial showing a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline, and three trials finding no difference between medications. In the only trial to assess the combination of dornase alfa with another medication compared to dornase alone, there was no benefit seen with the combination of dornase alfa and mannitol. Evidence of dornase alfa compared to other medications was limited and the open-label design of the trials may have induced bias, therefore the quality of the evidence was judged to be low.Dornase alfa did not cause significantly more adverse effects, 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 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 hyperosmolar agents in improving lung function.
Topics: Adolescent; Child; Child, Preschool; Cystic Fibrosis; Deoxyribonuclease I; Expectorants; Humans; Infant; Mannitol; Randomized Controlled Trials as Topic; Recombinant Proteins; Saline Solution, Hypertonic
PubMed: 27043279
DOI: 10.1002/14651858.CD001127.pub3