title: Survival of outborns with congenital diaphragmatic hernia: the role of protective ventilation, early presentation and transport distance: a retrospective cohort study.
abstract: BACKGROUND
  Congenital diaphragmatic hernia (CDH) is a congenital malformation associated with life-threatening pulmonary dysfunction and high neonatal mortality. Outcomes are improved with protective ventilation, less severe pulmonary pathology, and the proximity of the treating center to the site of delivery. The major CDH treatment center in Croatia lacks a maternity ward, thus all CDH patients are transferred from local Zagreb hospitals or remote areas (outborns). In 2000 this center adopted protective ventilation for CDH management. In the present study we assess the roles of protective ventilation, transport distance, and severity of pulmonary pathology on survival of neonates with CDH.
  
  
  METHODS
  The study was divided into Epoch I, (1990-1999, traditional ventilation to achieve normocapnia), and Epoch II, (2000-2014, protective ventilation with permissive hypercapnia). Patients were categorized by transfer distance (local hospital or remote locations) and by acuity of respiratory distress after delivery (early presentation-occurring at birth, or late presentation, ≥ 6 h after delivery). Survival between epochs, types of transfers, and acuity of presentation were assessed. An additional analysis was assessed for the potential association between survival and end-capillary blood CO2 (PcCO2), an indirect measure of pulmonary pathology.
  
  
  RESULTS
  There were 83 neonates, 26 in Epoch I, and 57 in Epoch II. In Epoch I 11 patients (42%) survived, and in Epoch II 38 (67%) (P = 0.039). Survival with early presentation (N = 63) was 48 % and with late presentation 95% (P <0.001). Among early presentation, survival was higher in Epoch II vs. Epoch I (57% vs. 26%, P = 0.031). From multiple logistic regression analysis restricted to neonates with early presentation and adjusting for severity of disease, survival was improved in Epoch II (OR 4.8, 95%CI 1.3-18.0, P = 0.019). Survival was unrelated to distance of transfer but improved with lower partial pressure of PcCO2 on admission (OR 1.16, 95%CI 1.01-1.33 per 5 mmHg decrease, P = 0.031).
  
  
  CONCLUSIONS
  The introduction of protective ventilation was associated with improved survival in neonates with early presentation. Survival did not differ between local and remote transfers, but primarily depended on severity of pulmonary pathology as inferred from admission capillary PcCO2.
authors.affiliation: Division of Neonatology, Department of Obstetrics and Gynecology, University Hospital Merkur, Zagreb, Croatia. sprungkatarina@hotmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Bojanić
authors.affiliation: Department of Pediatrics, University of Zagreb, School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia. enavia3@gmail.com.
authors.forename: Ena
authors.initials: E
authors.lastname: Pritišanac
authors.affiliation: Department of Pediatric Surgery, University of Zagreb, School of Medicine, University Hospital Centre, Zagreb, Croatia. tluetic@mef.hr.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Luetić
authors.affiliation: Department of Pediatrics, University of Zagreb, School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia. juricav1961@yahoo.com.
authors.forename: Jurica
authors.initials: J
authors.lastname: Vuković
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, MN, 55902, USA. sprung.juraj@mayo.edu.
authors.forename: Juraj
authors.initials: J
authors.lastname: Sprung
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, MN, 55902, USA. weingarten.toby@mayo.edu.
authors.forename: Toby N
authors.initials: TN
authors.lastname: Weingarten
authors.affiliation: Division of Neonatal Medicine, Mayo Clinic, Rochester, MN, USA. carey.william@mayo.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Carey
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA. schroedd@mayo.edu.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Schroeder
authors.affiliation: Department of Pediatrics, University of Zagreb, School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia. rcgrizelj@yahoo.com.
authors.forename: Ruža
authors.initials: R
authors.lastname: Grizelj
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D017523:Croatia / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D065630:Hernias, Diaphragmatic, Congenital / Q000150:complications / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007223:Infant; D007226:Infant Mortality / Q000639:trends; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis; D012121:Respiration, Artificial / Q000379:methods*; D012189:Retrospective Studies; D055502:Secondary Prevention / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014187:Transportation of Patients / Q000379:methods*