Improved Empirical Antibiotic Treatment of Sepsis After an Educational Intervention: The ABISS-Edusepsis Study

Ferrer R, Martínez ML, Gomà G, et al. Crit Care. 2018 Jun 22;22(1):167. [CrossRef] [PubMed]

Early appropriate antibiotic treatment is essential in sepsis. The authors evaluated the impact of a multifaceted educational intervention to improve antibiotic treatment. They prospectively studied all 2628 consecutive patients with sepsis/septic shock admitted to 72 intensive care units (ICUs) throughout Spain in two 4-month periods (before and immediately after the 3-month intervention). In the postintervention cohort, the mean (SD) time from sepsis onset to empirical antibiotic therapy was lower (2.0 (2.7) vs. 2.5 (3.6) h; p = 0.002), the proportion of inappropriate empirical treatments was lower (6.5% vs. 8.9%;p = 0.024), and the proportion of patients in whom antibiotic treatment was de-escalated was higher (20.1% vs. 16.3%; p = 0.004); the expected reduction in mortality did not reach statistical significance (29.4% in the postintervention cohort vs. 30.5% in the preintervention cohort; p = 0.544). The educational intervention is poorly described and the gains in time to empirical antibiotic therapy and inappropriate antibiotic are modest and did not result in an improvement in mortality. These make the authors’ conclusions that “educational interventions can still improve the delivery of care” uncertain.

Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial

Bergeron A, Chevret S, Granata A, et al. JAMA 2017;318(6):557-566. [CrossRef] [PubMed]

Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome presumably through an anti-inflammatory effect. The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who had undergone allogeneic HSCT for a hematological malignancy. Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen. Thirteen months after enrollment, the independent data and safety monitoring board stopped the trial. At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). The azithromycin group had increased mortality, with a 2-year survival of 56.6% (95% CI, 50.2%-63.7%) vs 70.1% (95% CI, 64.2%-76.5%) in the placebo group (unadjusted HR, 1.5; 95% CI, 1.1-2.0; P = .02). In a post hoc analysis, the 2-year cumulative incidence of hematological relapse was 33.5% (95% CI, 27.3%-39.7%) with azithromycin vs 22.3% (95% CI, 16.4%-28.2%) with placebo (unadjusted cause-specific HR, 1.7; 95% CI, 1.2-2.4; P = .002). The FDA recently issued a warning against using chronic azithromycin therapy in HSCT.

Depression, Antidepressant Use, and Risk of Venous Thromboembolism: Systematic Review and Meta-Analysis Of Published Observational Evidence

Kunutsor SK Seidu S, Khunti K. Ann Med. 2018 Jul 12:1-17. [CrossRef] [PubMed]

The authors conducted a systematic review and meta-analysis of published observational studies evaluating the associations of depression and antidepressant use with venous thromboembolism (VTE) risk. Eight observational studies with data on 960,113 non-overlapping participants and 9027 VTE cases were included. The pooled RR (95% CI) for VTE comparing antidepressant use with no antidepressant use was 1.27 (1.06-1.51). Tricyclic antidepressants, selective serotonin reuptake inhibitors and other antidepressants were each associated with an increased VTE risk; 1.16 (1.06-1.27), 1.12 (1.02-1.23), and 1.59 (1.21-2.09) respectively. In pooled analysis of three studies that compared patients with depression versus individuals without depression, the RR for VTE was 1.31 (1.13-1.53). The authors conclude that pooled observational evidence suggests that depression and use of antidepressants are each associated with an increased VTE risk. The effect of antidepressant drugs on VTE may be a class effect. The mechanistic pathways underlying these associations deserve further evaluation.

Electronic Health Records Associated with Lower Hospital Mortality After Systems Have Time to Mature

Lin SC, Jha AK, Adler-Milstein J. Health Aff (Millwood). 2018 Jul;37(7):1128-1135. [CrossRef] [PubMed]

The effect of electronic health record (EHR) adoption on mortality is mixed. The authors used data for the period 2008–13 to assess the relationship between EHR adoption and thirty-day mortality rates. They found that baseline adoption was associated with a 0.11-percentage-point higher rate per function. Over time, maturation of the baseline functions was associated with a 0.09-percentage-point reduction in mortality rate per year per function. Each new function adopted in the study period was associated with a 0.21-percentage-point reduction in mortality rate per year per function. They observed effect modification based on size and teaching status, with small and nonteaching hospitals realizing greater gains. Importantly, US hospitals that adopted EHRs had improved 30-day mortality rates compared to those hospitals that did not adopt EHRs. These findings suggest that implementation of EHRs lowers mortality but achieving a reduction in mortality will take time.

Sodium Bicarbonate Therapy for Patients with Severe Metabolic Acidaemia in the Intensive Care Unit (BICAR-ICU): A Multicentre, Open-Label, Randomised Controlled, Phase 3 Trial

Jaber S, Paugam C, Futier E, et al. Lancet. 2018 Jun 14. pii: S0140-6736(18)31080-8. [CrossRef] [PubMed]

Acute acidemia is frequently observed during critical illness. Sodium bicarbonate (bicarb) infusion for the treatment of severe metabolic acidemia is a possible treatment option but remains controversial and is not routinely recommended after cardiac arrest. The authors performed a multicenter, open-label, randomized controlled, phase 3 trial of bicarb in adult patients with severe acidemia (pH ≤7.20, PaCO2 ≤45 mm Hg) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. Death occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (p=0.24). However, in an a-priori defined group of patients with acute kidney injury the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significantly improved (63% vs 46%; p=0.0283). The authors conclude that in patients with severe metabolic acidemia, sodium bicarbonate had no effect on mortality but improved the day 28 mortality in patients with acute kidney injury.