Safety of 80% vs 30-35% fraction of inspired oxygen in patients undergoing surgery: a systematic review and meta-analysis.

BACKGROUND: Evidence-based guidelines from the World Health Organization (WHO) have recommended a high (80%) fraction of inspired oxygen (FiO2) to reduce surgical site infection in adult surgical patients undergoing general anaesthesia with tracheal intubation. However, there is ongoing debate over the safety of high FiO2. We performed a systematic review to define the relative risk of clinically relevant adverse events (AE) associated with high FiO2. METHODS: We reviewed potentially relevant articles from the WHO review supporting the recommendation, including an updated (July 2018) search of EMBASE and PubMed for randomised and non-randomised controlled studies reporting AE in surgical patients receiving 80% FiO2 compared with 30-35% FiO2. We assessed study quality and performed meta-analyses of risk ratios (RR) comparing 80% FiO2 against 30-35% for major complications, mortality, and intensive care admission. RESULTS: We included 17 moderate-good quality trials and two non-randomised studies with serious-critical risk of bias. No evidence of harm with high FiO2 was found for major AE in the meta-analysis of randomised trials: atelectasis RR 0.91 [95% confidence interval (CI) 0.59-1.42); cardiovascular events RR 0.90 (95% CI 0.32-2.54); intensive care admission RR 0.93 (95% CI 0.7-1.12); and death during the trial RR 0.49 (95% CI 0.17-1.37). One non-randomised study reported that high FiO2 was associated with major respiratory AE [RR 1.99 (95% CI 1.72-2.31)]. CONCLUSIONS: No definite signal of harm with 80% FiO2 in adult surgical patients undergoing general anaesthesia was demonstrated and there is little evidence on safety-related issues to discourage its use in this population.

Bone mineral density and fracture risk with long-term use of inhaled corticosteroids in patients with asthma: systematic review and meta-analysis.

OBJECTIVES: We aimed to assess the association between long-term use of inhaled corticosteroids (ICS) and bone adverse effects in patients with asthma. DESIGN: Systematic review and meta-analysis of fracture risk and changes in bone mineral density with long-term ICS use in asthma. METHODS: We initially searched MEDLINE and EMBASE in July 2013, and performed an updated PubMed search in December 2014. We selected randomised controlled trials (RCTs) and controlled observational studies of any ICS (duration at least 12 months) compared to non-ICS use in patients with asthma. We conducted meta-analysis of ORs for fractures, and mean differences in bone mineral density. Heterogeneity was assessed using the I(2) statistic. RESULTS: We included 18 studies (7 RCTs and 11 observational studies) in the systematic review. Meta-analysis of observational studies did not demonstrate any significant association between ICS and fractures in children (pooled OR 1.02, 95% CI 0.94 to 1.10, two studies), or adults (pooled OR 1.09, 95% CI 0.45 to 2.62, four studies). Three RCTs and three observational studies in children reported on bone mineral density at the lumbar spine, and our meta-analysis did not show significant reductions with ICS use. Three RCTs and four observational studies in adults reported on ICS use and bone mineral density at the lumbar spine and femur, with no significant reductions found in the meta-analysis compared to control. CONCLUSIONS: ICS use for ≥12 months in adults or children with asthma was not significantly associated with harmful effects on fractures or bone mineral density.

Impact of Inhaled Corticosteroids on Growth in Children with Asthma: Systematic Review and Meta-Analysis.

BACKGROUND: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. METHODS: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. RESULTS: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). CONCLUSION: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users.

Meta-review: adverse effects of inhaled corticosteroids relevant to older patients.

BACKGROUND: In recent years, clinical trials and observational studies have raised concerns about the potential adverse effects of inhaled corticosteroids (ICS) such as pneumonia, cataract, fractures and hyperglycaemia, which are of particular concern for older patients. METHODS: We conducted a meta-review by searching electronic databases (MEDLINE, EMBASE, PubMed) for systematic reviews and meta-analyses of ICS use and the adverse effects of interest. We also evaluated new primary studies that reported information beyond that available from previously published meta-analyses. Two reviewers independently extracted data on measures of associated harm with ICS use. RESULTS: We identified five relevant meta-analyses for inclusion in this meta-review, and also three new studies of ICS and pneumonia. We found consistent evidence of a dose-response relationship between ICS use and serious adverse effects such as fractures and pneumonia. The estimated number needed to treat for harm due to fracture with ICS was 83 with 3-years use, and 60 per year for pneumonia. Both asthma and chronic obstructive pulmonary disease (COPD) users of ICS were at risk of pneumonia, with fluticasone appearing to confer higher risk than budesonide. There is also some suggestion that ICS use is associated with cataracts in a dose-response manner but the evidence is less robust here. Equally, the influence of ICS on diabetes mellitus remains uncertain. CONCLUSIONS: In view of the dose-response relationship seen between ICS use and important adverse effects such as fractures and pneumonia, clinicians needs to carefully balance the benefits of ICS versus the harms in older patients receiving long-term high-dose ICS.