Development of Pneumonia Due to Alveolar Glucose Levels in Systemic Hyperglycemia
Conditions: Glucose Metabolism Disorders, Pneumonia, Bacterial
Sponsor: University of Ulm

Study Protocol Version 2 – 08/2017 
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Study Protocol 
 
 
 
Development of Pneumonia Due to Alveolar 
Glucose Levels in Systemic Hyperglycemia 
 
 
 
Version:              2 
Date:   
08/01/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol Version 2 – 08/2017 
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1. General study design: 
Monocentric prospective clinical observational study 
 
2. Schedule: 
Inclusion of the first patient:  
 
08/01/2017 
Inclusion last patient:  
 
 
12/31/2018 
Close the database:  
 
 
01/31/2019 
End of the statistical evaluation:   
06/31/2019 
 
3. Study endpoint, duration of study: 
The primary endpoint of the study is the incidence of pneumonia 
 
4. Sample size calculation: 
The sample size estimate was based on the assumption that in the investigated 
patient population the occurrence of pneumonia could be expected in 10% of the 
patients. Thus, for an unconnected sample, a ratio (m) of 0.9 controls per 
incidence of pneumonia. In a previous study (Bacterial respiratory tract infections 
are promoted by systemic hyperglycemia after severe burn injury in pediatric 
patients, Kraft et al., Burns, 2014, May), it was found that the mean values (δ) of 
both groups for glucose  differed by about 30 mg / dL in the mean with a standard 
deviation (σ) of 20 mg / dL. Under the same conditions, 14 controls and 16 
patients with pneumonia are needed to reject the null hypothesis with a probability 
(power) of 0.9. 
The occurrence of the first type error (α) was set at 0.01. Design: Independent 
α = 0.01; power = 0.9; δ = 30; σ = 20; m = 0.9; n =16; 
t-test confidence interval width = 40.68604 
Calculated with PS Power and Samplesize Calculator Version 3.0, 
http://biostat.mc.vanderbilt.edu/PowerSampleSize 
 
5. Selection of the study population: 
Patients undergoing elective cardiac surgery matching inclusion and exclusion 
criteria 
 
6. Subsequent exclusion of study patients: 
Reasons for a subsequent exclusion of the patient only apply if subsequently it is 
determined that not all inclusion criteria are met or exclusion criteria that were not 
initially recognized. These patients are also excluded from the documentation. 
 
7. Documentation / Evaluation: 
All study-relevant data are recorded in the provided documentation sheets by the 
responsible study physicians and, if necessary, the study assistants. The study 
forms are digitized and stored in the in-house EDP system in compliance with the 
safety guidelines using the programs Microsoft Excel® and Access®. Radiological 
images are stored in digital form, preferably in TIFF or raw data format. The 
statistical analysis is carried out by means of the programs Sigmastat® and 
Sigmaplot®. 
The statistical evaluation is carried out on the one hand with regard to the cut-off 
value of the glucose threshold of the lung by means of Receiver Operating 
Characteristic (ROC). This is used to validate our findings in comparison to the 
already existing preliminary studies. The evaluation of dichotomous variables is 
performed by Chi Square Test or, if necessary, by Logistic Regression Analysis. 

Study Protocol Version 2 – 08/2017 
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Constant features are compared using Student's t-test, analysis of variance 
between the groups. With regard to the presence of disturbing variables between 
the two groups, the formation of subgroups, possibly a matching by means of a 
propensity score, is planned. 
 
8. Study plan: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients will be included in the study, if fulfilling the inclusion criteria and missing 
exclusion criteria. Written informed consent will be obtained from the patients. 
Patients will be pseudonymyised by assigning a sequential number. 
Anonymization of the patients cannot be considered in such a conceived study, 
since the change of personal data makes an assignment of essential clinical 
course data impossible. 
 
Blood draws: 
Blood will be collected by puncture or draw by venous or arterial catheter during 
the clinical routine for determination of leucocyte count, CRP value, and blood 
sugar. Blood samples will be analyzed in the in-house laboratory. Blood sugar 
levels are additionally measured in the intensive care unit using a blood gas 
analyzer. 
In addition, one blood sample EDTA and one serum are collected (9 mL each). 
The centrifugation and aliquoting of the obtained plasma and serum samples will 
be spinned down and aliquoted. The samples are stored at -80 ° C in the 
laboratory rooms of the Cardiac Surgery Department for later analysis. 
 
X-ray: 
The evaluation of the radiological images of the chest is carried out as part of the 
clinical requirements. There is no additional requirements of radiological 
examinations due to the study. 
 
Timepoint 1, preoperative: 
Obtaining informed consent and inclusion in the 
study, blood draw 
Preoperative chest X-ray (clinical routine) 
Timepoint 2, Operative Intervention: 
Blood draw, asservation of alveolar secretions 
(endobronchial after intubation) 
Timepoints 3.1 – 3.n, postoperative (daily): 
Blood draw, asservation of alveolar secretions (if 
ventilated) chest X-ray (if clinically needed) 
Timepoint 4, Discharge: 
Final evaluation 

Study Protocol Version 2 – 08/2017 
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Endobronchial sampling: 
 
The endobronchial sampling of alveolar fluid will be performed by utilizing the 
inserted tube and aspiration with a suction catheter. Two samples are taken. The 
first sample is sent to the in-house laboratory immediately after sampling for 
microbiological analysis. The second sample is stored at -80 ° C in the premises 
of the cardiosurgical research department until later analysis. 
 
Clinical evaluation/examination: 
There is a daily clinical examination of the patients for signs of pneumonia.