Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial.

OBJECTIVE: To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery. DESIGN: Phase III, randomised, double blind, placebo controlled trial. SETTING: 34 centres in France, December 2017 to March 2019. PARTICIPANTS: 1222 adults (>50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months. INTERVENTIONS: Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure. MAIN OUTCOMES MEASURES: The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered). RESULTS: Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46). CONCLUSIONS: Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT03218553.

Effect of topical pressure-lowering medication on prevention of intraocular pressure spikes after intravitreal injection.

Purpose. The aim of this study was to evaluate pressure increases after intravitreal injections (IVI) and the interest in using prophylactic pressure-lowering medications. 
Methods. This was a prospective study of 250 anti-vascular endothelial growth factor IVI (ranibizumab) divided into 5 groups of 50 IVI (group 1: no intraocular pressure [IOP]-lowering medication; group 2: apraclonidine 1%; group 3: acetazolamide; group 4: fixed association brimonidine + timolol; group 5: fixed association dorzolamide + timolol). The IOP was measured before, immediately after (T1), 15 minutes after (T15), and 45 minutes after (T45) the IVI using a tonometer. The data were analyzed by analysis of variance followed by a Bonferroni as post hoc test if necessary.
Results. The mean IOP peak in group 1 was 46.4±10 mmHg at T1, 21.7±10.2 mmHg at T15, and 15.4±8.6 mmHg at T45. It was not correlated with axial length (r=0.04, p=0.81) or lens status (phakic vs pseudophakic: p=0.88). A mild but significant correlation was found with age (r=0.36, p=0.006). Topical medications produced a significant reduction of IOP at every time point, of around 9 mmHg at T1. The reduction in IOP obtained with acetazolamide was not significant at T1 (-1.6 mmHg, p=0.12), but became significant at T15 and T45 (p=0.011 and p=0.015). 
Conclusions. Intraocular pressure spike was high but transient. Topical medications, however, produced a significant reduction in IOP spike as well as in the duration of the increased pressure. It would be advisable to prevent this IOP spike, especially when procedures are repeated, notably in patients with glaucoma.