Reparixin improves survival in critically ill and transplant patients: A meta-analysis.

BACKGROUND: Reparixin, an anti-inflammatory drug that inhibits interleukin 8 (IL-8) activity, might be life-saving for high-risk in-hospital patients without increasing the risk of infection according to a previous meta-analysis. With the increasing availability of randomised data the aim of the current study is to update previous findings by including any randomised control trials (RCTs) investigating the impact of reparixin on survival of critically ill or transplant patients. METHODS: A search strategy was developed to identify all RCTs involving reparixin in critically ill or transplant patients, with the exclusion of oncological patients. Two trained and independent authors conducted a thorough search of relevant databases. In addition, backward snowballing was employed. Language restrictions were not imposed. RESULTS: Our analysis included a total of nine studies involving 733 patients: 437 received reparixin and 296 the comparator. The reparixin group had a significantly lower all-cause mortality rate compared to the control group [15/437 (3.4%) vs. 19/294 (6.4%), odds ratio = 0.47 (95% confidence interval 0.23-0.96), p-value for effect .04, I2 = 22%, number needed to treat = 33]. These findings had the same direction and magnitude of effect across COVID-19 patients (n = 325) and non-COVID-19 patients (n = 408). Furthermore, there were no significant differences in the rate of pneumonia, sepsis or non-serious infections between the two groups. CONCLUSIONS: The findings of this meta-analysis indicate that reparixin, an anti-inflammatory drug, improved survival in critically ill or transplant patients (including both COVID-19 and non-COVID-19 patients) without increasing the risk of infection.

Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials.

PURPOSE: We performed a meta-analysis of randomized controlled trials to evaluate if etomidate impacted mortality in critically ill adults when compared with other induction agents. MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials which compared etomidate with any other induction agent in critically ill adult patients undergoing endotracheal intubation. The primary outcome was mortality at the main timepoint defined by the study. We conducted a fixed-effects meta-analysis for the risk ratio. Using that risk ratio and 95% confidence interval, we then estimated the probability of any harm (RR > 1) and the number needed to harm ≤100 (RR ≥ 1.05). RESULTS: We included 11 randomized trials comprising 2704 patients. We found that etomidate increased mortality (319/1359 [23%] vs. 267/1345 [20%]; risk ratio (RR) = 1.16; 95% confidence interval (CI), 1.01-1.33; P = 0.03; I2 = 0%; number needed to harm = 31). The probabilities of any increase and a 1% increase (NNH ≤100) in mortality were 98.1% and 92.1%, respectively. CONCLUSIONS: This meta-analysis found a high probability that etomidate increases mortality when used as an induction agent in critically ill patients with a number needed to harm of 31.

The effect of reparixin on survival in patients at high risk for in-hospital mortality: a meta-analysis of randomized trials.

Introduction: A great number of anti-inflammatory drugs have been suggested in the treatment of SARS-CoV-2 infection. Reparixin, a non-competitive allosteric inhibitor of the CXCL8 (IL-8) receptors C-X-C chemokine receptor type 1 (CXCR1) and C-X-C chemokine receptor type 2 (CXCR2), has already been tried out as a treatment in different critical settings. Due to the contrasting existing literature, we decided to perform the present meta-analysis of randomized controlled trials (RCTs) to investigate the effect of the use of reparixin on survival in patients at high risk for in-hospital mortality. Methods: We created a search strategy to include any human RCTs performed with reparixin utilization in patients at high risk for in-hospital mortality, excluding oncological patients. Two trained, independent authors searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for appropriate studies. Furthermore, references of review articles and included RCTs were screened to identify more studies. No language restrictions were enforced. To assess the risk of bias of included trials, the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) was used. Results: Overall, six studies were included and involved 406 patients (220 received reparixin and 186 received the comparator). The all-cause mortality in the reparixin group was significantly lower than that in the control group [5/220 (2.3%) in the reparixin group vs. 12/186 (6.5%) in the control group, odds ratio = 0.33 (95% confidence interval 0.12 to 0.96), p-value for effect 0.04, p for heterogeneity 0.20, I2 = 36%]. In addition, no difference in the rate of pneumonia, sepsis, or non-serious infections was shown between the two groups. Conclusion: Our meta-analysis of randomized trials suggests that short-term inhibition of CXCL8 activity improved survival in patients at high risk for in-hospital mortality without increasing the risk of infection. Meta-analysis registration: PROSPERO, identifier CRD42021254467.