Effect of sodium bicarbonate on functional outcome in patients with out-of-hospital cardiac arrest: a post-hoc analysis of a French and North-American dataset.

BACKGROUND AND IMPORTANCE: No large randomised controlled trial has assessed the potential benefits on neurologic outcomes of prehospital sodium bicarbonate administration in patients with nontraumatic out-of-hospital cardiac arrest (OHCA). OBJECTIVE: To obtain information of assistance in designing a randomised controlled trial of bicarbonate therapy after OHCA in specific patient subgroups. DESIGN: We conducted two, separate, simultaneous, retrospective studies of two distinct, unlinked datasets. SETTING AND PARTICIPANTS: One dataset was a French nationwide population-based registry (RéAC Registry, French dataset) and the other was a randomised controlled trial comparing continuous to interrupted chest compressions in North America (ROC-CCC trial, North-American dataset). INTERVENTION: We investigated whether prehospital bicarbonate administration was associated with better neurologic outcomes. OUTCOME MEASURES AND ANALYSES: The main outcome measure was the functional outcome at hospital discharge. To adjust for potential confounders, we conducted a nested propensity-score-matched analysis with inverse probability-of-treatment weighting. MAIN RESULTS: In the French dataset, of the 54 807 patients, 1234 (2.2%) received sodium bicarbonate and 450 were matched. After propensity-score matching, sodium bicarbonate was not associated with a higher likelihood of favourable functional outcomes on day 30 [adjusted odds ratio (aOR), 0.912; 95% confidence interval (95%CI), 0.501-1.655]. In the North-American dataset, of the 23 711 included patients, 4902 (20.6%) received sodium bicarbonate and 1238 were matched. After propensity-score matching, sodium bicarbonate was associated with a lower likelihood of favourable functional outcomes at hospital discharge (aOR, 0.45; 95% CI, 0.34-0.58). CONCLUSION: In patients with OHCA, prehospital sodium bicarbonate administration was not associated with neurologic outcomes in a French dataset and was associated with worse neurologic outcomes in a North-American dataset. Given the considerable variability in sodium bicarbonate use by different prehospital care systems and the potential resuscitation-time bias in the present study, a large randomised clinical trial targeting specific patient subgroups may be needed to determine whether sodium bicarbonate has a role in the prehospital management of prolonged OHCA.

A murine model to study the gut bacteria parameters during complex antibiotics like cefotaxime and ceftriaxone treatment.

BACKGROUND: The globally increasing resistance due to extended-spectrum beta-lactamase producing Enterobacteriaceae is a major concern. The objective of this work was to develop a murine model to study the gut bacteria parameters during complex antibiotics like cefotaxime and ceftriaxone treatment and to compare the fecal carriage of ESBL-producing Enterobacteriaceae. METHODS: SWISS mice were treated either with ceftriaxone or with cefotaxime or with NaCl 0.9% as a control group from day 1 to day 5. We performed a gavage at day 4 with a Klebsiella pneumonia CTX-M9. We collected stools and performed pharmacological measurements, cultures and 16S rRNA gene amplification and sequencing during the 12 days of the stool collection. RESULTS: Mice treated with ceftriaxone were more colonized than mice treated with cefotaxime after gavage (p-value = 0.008; Kruskal-Wallis test). Ceftriaxone and cefotaxime were both excreted in large quantity in gut lumen but they drove architecture of the gut microbiota in different trajectories. Highest levels of colonization were associated with particular microbiota composition using principal coordinate analysis (PCoA) which were more often achieved in ceftriaxone-treated mice and which were preceded by highest fecal antibiotics concentrations in both cefotaxime or ceftriaxone groups. Using LEfSe, we found that twelve taxa were significantly different between cefotaxime and ceftriaxone-treated mice. Using SplinectomeR, we found that relative abundances of Klebsiella were significantly higher in CRO than in CTX-treated mice (p-value = 0.01). CONCLUSION: Ceftriaxone selects a particular microbial community and its substitution for cefotaxime could prevent the selection of extended-spectrum beta-lactamase producing Enterobacteriaceae.