Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial.

BACKGROUND: Hospital-acquired pneumonia is common after traumatic brain injury, and might be partly a result of traumatic brain injury-induced adrenal insufficiency. We tested the efficacy of low-dose hydrocortisone with fludrocortisone for the prevention of hospital-acquired pneumonia. METHODS: We did this double-blind, phase 3, placebo-controlled trial in 19 intensive care units in France. We enrolled patients aged 15-65 years in the first 24 h after severe traumatic brain injury (Glasgow coma scale score ≤8 and trauma-associated lesion on brain CT scan). Patients were randomly assigned (1:1; fixed blocks of 12, stratified by centre and mechanism, Glasgow coma scale, age, and arterial pressure [MGAP] score) to receive either hydrocortisone (200 mg per day tapered) and fludrocortisone (50 µg tablet once per day) or matching placebo for 10 days. Before receiving study drug, adrenal function was assessed with a short corticotropin test. Treatment was stopped if patients had no adrenal insufficiency. The primary outcome was the occurrence of hospital-acquired pneumonia within 28 days after randomisation. We did an intention-to-treat analysis and a modified intention-to-treat analysis including only patients with adrenal insufficiency (adjusted for etomidate use). This study is registered with ClinicalTrials.gov, number NCT01093261. FINDINGS: From Sept 1, 2010, to Nov 29, 2012, we enrolled 336 patients (168 assigned to each group). Eight patients withdrew consent. At day 28, 74 of 165 patients (45%) in the steroid group and 87 of 163 (53%) in the placebo group had developed one or more episodes of hospital-acquired pneumonia (hazard ratio [HR] 0.75; 95% CI 0.55-1.03, p=0.07). In intention-to-treat analysis, we recorded 86 episodes of hospital-acquired pneumonia in the steroid group versus 110 in the placebo group (median 0, IQR 0-1 vs median 1, IQR 0-1 cases per patient, p=0.07). In modified intention-to-treat analyses, the HR for hospital-acquired pneumonia with steroids versus placebo was 0.80 (95% CI 0.56-1.14, p=0.22) in patients with adrenal insufficiency, and, in an exploratory preplanned analysis, 0·48 (0·23-1·01; p=0·05) in patients with normal adrenal function. We recorded no adverse events related to treatment. INTERPRETATION: Low-dose hydrocortisone with fludrocortisone did not improve the outcome of patients with traumatic brain injury. However, the study was underpowered because the proportion of patients with hospital-acquired pneumonia in the placebo group was lower than expected. The results were close to statistical significance for efficacy, meaning that further studies are therefore needed. FUNDING: Société Française d'Anesthésie Réanimation.

Placenta accreta: management with uterine artery embolization in 17 cases.

PURPOSE: To report on the management of placenta accreta with uterine artery embolization (UAE) and to analyze the outcomes. MATERIALS AND METHODS: A retrospective study was performed over a 128-month period of all women with placenta accreta who underwent UAE in a single center. Seventeen patients were included, and they were further divided into two groups: a preventive group (diagnosis was made in the prenatal period, n = 6) and a curative group (diagnosis was made during delivery, n = 11). The mean patient age was 34.6 years +/- 5.5 in the preventive group and 31.4 years +/- 4.3 in the curative group. The mean term of pregnancy was 35 weeks +/- 2 of amenorrhea in the preventive group and 38 weeks +/- 2 in the curative group. RESULTS: The primary success of embolization was 100% in both groups. In the preventive group, massive bleeding occurred in a patient 2 days after unsuccessful manual placenta delivery resulted in an hysterectomy; in a second case, delayed bleeding (2 months after the procedure) was controlled with a second embolization. There were no episodes of repeat bleeding in the curative group. In the preventive group, two patients presented with uterine scarring, with synechiae in one and endometrial atrophy in the other. In the curative group, one patient presented with secondary amenorrhea. The delay before embolization was significantly different in the two groups (23.3 minutes +/- 5.1 in the preventive group vs 73 minutes +/- 44.7 in the curative group, P < .01), and total blood loss was 0.7 L +/- 0.8 in the preventive group and 2.6 L +/- 1.2 in the curative group (P < .01). CONCLUSIONS: Prenatal diagnosis of placenta accreta permits its preventive management, which reduces time to embolization and blood loss.