目的:心搏骤停患者常发生呼吸机相关性肺炎(VAP)。心脏骤停后VAP的诊断仍然具有挑战性,而目前的生物标志物如C反应蛋白(CRP)或降钙素原(PCT)的使用存在争议。
目的:评估生物标志物对帮助心脏骤停后VAP诊断的影响。
方法:这是一项随机的前瞻性辅助研究,多中心,治疗性低温治疗pRevenT感染性并发症(ANTHARTIC)试验期间的双盲安慰剂对照抗生素治疗评估了抗生素预防对预防VAP的影响在院外患者继发于可电击心律的心脏骤停和治疗性低温治疗中.裁决委员会根据预定义的临床盲目评估VAP,放射学,和微生物标准。所有具有可用生物标志物的患者,样本,和同意批准包括在内。
方法:主要终点是评估生物标志物在采样后48小时内正确诊断和预测VAP的能力。次要终点是研究两种生物标志物在区分VAP中的组合。在第3天的基线处收集血液样品。盲目地进行炎症生物标志物测量的常规和探索性小组。对随机分组的分析进行了调整。
结果:在161名具有可用生物样本的ANTHARTIC试验患者中,患有VAP的患者(n=33)具有较高的体重指数和急性生理学和慢性健康评估II评分,更多没有目击的心脏骤停,更多的儿茶酚胺,与没有VAP的患者相比,治疗性低温持续时间更长(n=121)。在单变量分析中,与VAP显著相关并显示曲线下面积(AUC)大于0.70的生物标志物是CRP(AUC=0.76),白细胞介素(IL)17A和17C(IL17C)(0.74),巨噬细胞集落刺激因子1(0.73),PCT(0.72),血管内皮生长因子A(VEGF-A)(0.71)。结合新型生物标志物的多变量分析显示,有几对p值小于0.001,比值比大于1:VEGF-A+IL12亚基β(IL12B),Fms相关酪氨酸激酶3配体(Flt3L)+C-C趋化因子20(CCL20),Flt3L+IL17A,Flt3L+IL6,STAM结合蛋白(STAMBP)+CCL20,STAMBP+IL6,CCL20+4EBP1,CCL20+caspase-8(CASP8),IL6+4EBP1和IL6+CASP8。观察到CRP+IL6的最佳AUC(0.79),CRP+CCL20(0.78),CRP+IL17A,和CRP+IL17C。
结论:我们的探索性研究表明,特定的生物标志物,尤其是CRP联合IL6有助于更好地诊断或预测心脏骤停患者早期VAP的发生。
OBJECTIVE: Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated.
OBJECTIVE: To evaluate biomarkers\' impact in helping VAP diagnosis after cardiac arrest.
METHODS: This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included.
METHODS: The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group.
RESULTS: Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C-C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C.
CONCLUSIONS: Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.