The retrospective and anonymized data collection and analyses were conducted in accordance with local government law (Hamburg Hospital Act [Hamburgisches Krankenhausgesetz] Sect. 12) without the requirement for approval or informed consent. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Study design

This study was a retrospective, single-center, exploratory cohort-study.

Setting and population

The study was conducted in the Department of Intensive Care, University Medical Center, Hamburg-Eppendorf with twelve intensive care units (surgical, medical, neurological, and interdisciplinary) and a total of 140 beds. Adult patients were included if they had received tracheal intubation in the intensive care unit for clinical indication and had been mechanically ventilated for more than 48 h. Patients were included from January 1, 2018, to December 31, 2020. Patients receiving intubation exclusively for surgery or other procedures were excluded. According to the route of intubation, patients were categorized into either the nasotracheal intubation group (NTI) or the orotracheal intubation group (OTI). Repeated intubations in individual patients were assessed, but only the last episode of intubation and ventilation was included in the analysis of time and outcome variables. For the purpose of patient characterization and adjustment of the analyses, patients were grouped as surgical, neurological, medical with community acquired pneumonia, and other medical patients.

Outcome parameters

The primary endpoint was the depth of sedation defined as fraction of time with a Richmond-Agitation-Sedation-Scale (RASS) of 0 or − 1 on the first day after intubation to end of day 3. Secondary endpoints were the mean RASS score, doses of vasopressors and sedative medication, proportion of spontaneous breathing, mobilization with physiotherapy assessed by the ICU-mobility scale11, rates of successful extubation and tracheostomy, length of ventilation, and complications such as incidence of ventilator acquired pneumonia (VAP), and sinusitis. VAP and sinusitis were defined according to the Center Disease Control and Prevention (CDC) criteria. The observation period was until extubation or up to a maximum of ten days after intubation, whatever occurred first. Successful extubation was defined as discharged alive from ICU without prior requirement for tracheostomy.

Weaning from the ventilator was guided by standard operating procedure. All patients received a spontaneous breathing trial daily after weaning readiness was reached, followed by predefined weaning steps corresponding to predefined lengths of spontaneous breathing. A RASS of − 1 was aimed for with the least possible dose of sedatives, but still ensuring adequate tolerance to the endotracheal tube. RASS was obtained by the nursing staff at least three times daily and documented in the electronic record.

The ICU mobility scale includes scores from 0 (passive exercise by staff, patient not actively moving) to 10 (walking independently without a gait aid) with (1) exercises in bed, (2) patient passively moved to chair, (3) sitting over edge of bed, (4) standing, (5) transfer bed to chair, (6) marching on spot at bedside, and scores above (7) walking away from bed.

The length of ventilation, rates of successful extubation and tracheostomy were obtained from the last instance of intubation.

Data retrieval

Data were obtained anonymized from the patient data management system (Intensive Care Manager V10 and the associated data extraction tool ICMiq V1.3, both Drägerwerk AG, Lübeck, Germany) in the Department of Intensive Care Medicine (University Medical Center Hamburg-Eppendorf, Germany). Data were managed with Microsoft Excel 365 and Visual Basic V7.1 (both Microsoft Inc., Redmond, WA, USA).


Statistical analyses were performed using SPSS (version 27, IBM Inc., Armonk, NY, USA). We used t-tests, Welsh tests, Fisher’s Exact tests, binary multivariable logistic regression analyses, and generalized mixed model analyses, as applicable. For the logistic regression analyses, parameters differing with a p-value < 0.1 between the groups were tested as covariates. Furthermore, we conducted sensitivity analyses included only patients with one instance of intubation, excluding patients’ diagnoses, including COVID-19 disease as a separate group, and excluding patients suffering from COVID-19 from the analysis.

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