Clinical trial NCT02337673: Screening of Postoperative Pulmonary Complications by Electrical Impedance Tomography
Official title: Screening of Postoperative Pulmonary Complications by Electrical Impedance Tomography in Intensive Care Patients Undergoing Epigastric Surgery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Disease
Postoperative Respiratory Complications
Malignant Neoplasm of Stomach
Liver Diseases
Pancreatic Diseases
Keywords: Postoperative Pulmonary Complication
Electrical Impedance Tomography
Splenectomy
Gastric surgery
Gastrectomy
Pancreatic surgery
Pancreatectomy
Liver surgery
Hemihepatectomy
Cholecystectomy
Acute Respiratory Distress Syndrome
Hypoxemia
Atelectasis
Pulmonary obstruction
Pneumonia
Pneumothorax
Pleural effusion
Pulmonary edema
Lead sponsor: Johannes Gutenberg University Mainz
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients of a primary care clinic (university hospital) undergoing elective epigastric surgery by laparotomy in general anesthesia with elective postoperative intensive care surveillance.

Brief summary: The purpose of this study is to determine whether Electrical Impedance Tomography can be used as sensitive and specific predictor in the detection of postoperative pulmonary complications (e.g. pneumonia, bronchitis, acute respiratory distress syndrome, pleural effusion, pneumothorax, pulmonary edema, atelectasis, pulmonary embolism, hypoxemia, hypercapnia, spasms and obstructions of the airway) in patients undergoing epigastric surgery.

Detailed description: * Study cycle:

  1. Check of criteria of inclusion/exclusion
  2. Informed consent
  3. Recording preoperative data via paper case report form
  4. Preoperative EIT measurement
  5. Postoperative EIT measurement
  6. Recording postoperative data via paper case report form

     Patients therapy and any diagnostic investigation during hospital stay (apart from EIT measurement) are performed appropriate to patients individual clinical needs and are independent from participation in this clinical trial. As PPC may result from surgical complications (e.g. intra- /postoperative bleeding, anastomotic leak, infection of the wound, injury of neighboring organs) they are monitored.
* Statistical analysis:

Sample size:

After consultation of Johannes-Gutenberg-University Institute of Medical Biometry and Epidemiology the following procedure was developed: Pre-analysis with 20 patients, then determination of definitive sample size (advised 80 patients).

Population:

Any registered patient is included in population even if no study-treatment was performed. To fulfill Pre-Protocol-Population-criteria EIT-measurement has to be performed before and after elective epigastric surgery and information about PPC must be revealable from patients medical file/records.

* Analysis of efficacy:

  1. Primary objective:

     (A) Incidence of any PPC (postoperative pulmonary complication) until postoperative day 7; Acquisition of PPC might require diagnostic investigation during hospital stay; investigations are only performed appropriate to patients individual clinical needs. As PPC are defined:
     * I: desaturation, increased oxygen demand (data from electronic health record)
     * II: dys-/atelectasis, pleural effusion, pneumothorax, pulmonary vein congestion (data from thoracic x-ray)
     * III: detected respiratory infection/pneumonia, pulmonary edema, Aspiration, non-invasive/CPAP-Ventilation, necessity of pleural drain/of bronchoscopy (data from electronic health record, x-ray)
     * IV: Reintubation (data from electronic health record), ARDS (according to Berlin Definition)

     (B) regional Distribution of Ventilation (Analysis of EIT raw data pre- and postoperative in 4 regions of interest: ventral, mid-ventral, mid-dorsal, dorsal; correlation between PPC and difference in regional Distribution of Ventilation at defined moment)
  2. Secondary objective: post-hoc Analysis (see down Secondary Outcome Measure)

     Average, Median, Quartile, Standard Deviation are detected and shown in Box-plots (type of graphic). Explorative comparison of parameters is effected by t-Test, Mann-Whitney-U-Test, Fisher-Test dependent on normal distribution.
* Quality assurance and data management Design, execution and analyzation of the study is ICH-GCP-conform (Good-Clinical-Practice-Guideline of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use). All responsible persons are obliged to good clinical practice. All changes in study protocol are to be authorized by responsible Ethics Committee. The P.I. is responsible for source data verification to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources (e.g., medical records, paper or electronic case report forms).

Prior to written informed consent all patients are to be informed about character and consequences of the study. With their signature patients permit collection and use of source data. Every patient receives an Identification code for pseudonymization of data. Analyzation and publication of data is effected anonymously only. Data collection is mainly provided in an electronic data base, besides in a paper-based Case Report Form. All electronic and paper-based data and archived in our Clinical Research Center and are accessible for authorized persons (Monitor, Auditor). The study protocol does not provide audits.

Amendment after Pre-analysis:

We conducted a preliminary study of 23 patients for sample size calculation, aligned with the goal of predicting probability of relevant PPC. Power calculation was based on the assumption that 50 % of patients would develop relevant PPC. We performed a power analysis using the Wilcoxon test. The assumption was that AUC of EIT-parameters for distinguishing PPC-affected patients from non-affected patients would be at least 0.65. In order to demonstrate that AUC is indeed above 0.5, a Wilcoxon test can be applied. AUC=0.65 translates into P(X\<Y)=0.65. To demonstrate this at the 5%-significance level with a power of 80%, 116 patients are needed. Considering that approximately 10% of patients may not be evaluable, a total sample size of 130 patients was determined. Interim analysis revealed, that incidence of relevant PPC in the study cohort was lower than assumed in sample size calculation. Therefore a higher sample size was necessary than expected. Furthermore, recruiting was slow. We therefore switched from a confirmatory to a descriptive approach.

Eligibility criteria: Inclusion Criteria:

* age \> 17 years
* no participation in another trial
* mental and physical state allow written consent
* elective epigastric surgery by laparotomy in general anesthesia (e.g. gastrectomy, splenectomy, pancreatic surgery, liver surgery/hemihepatectomy, cholecystectomy)

Exclusion Criteria:

* age \< 18 years
* in women: pregnancy
* missing or disability for giving written consent
* emergency patients
* patients after cardiac surgery less than 3 months ago
* patients after pulmonary lobectomy during lifetime
* patients with cardiac stimulator/defibrillator or any other implant with electric activity
* patients with cutaneous lesions or bandage in the area of EIT electrode placement
* patients with instability of the spine
* body mass index \> 50

Primary outcomes:
measure: Change of regional ventilation partition (ROI analysis in 8 pulmonary ROIs) from preoperative to postoperative state.
timeFrame: 1.) First EIT-measure: Preoperative Day; 2.) Second EIT-measure: Day of Operation (after extubation) or in between Postoperative Day 1-7 (in case of deferred extubation)
Secondary outcomes:
measure: Postoperative EIT-measured regional ventilation distribution (ROI analysis in 8 pulmonary ROIs)
timeFrame: 1 week
measure: Postoperative EIT-measured regional ventilation distribution (ROI analysis in 8 pulmonary ROIs)
timeFrame: 1 week
measure: Appearance of all specific forms of PPC (Postoperative Pulmonary Complications) within postoperative day 1-7
timeFrame: 1 week
measure: Outcome (e.g. mortality, time of intensive care therapy, ventilator-obligatory-free days on Postoperative Day 1-7 Postoperative EIT-measure is predictive for patients outcome
timeFrame: 1 week
measure: Time of intensive care therapy
timeFrame: 1 week
measure: Ventilator-obligatory-free days
timeFrame: 1 week
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz, Klinik für Anästhesiologie (University Hospital of Johannes Gutenberg-University Mainz, Department of Anesthesiology)
state: Rheinland-Pfalz (Rhineland-Palatinate)
Study officials:
affiliation: marc-bodenstein@gmx.de
name: Marc Bodenstein
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bodenstein M, David M, Markstaller K. Principles of electrical impedance tomography and its clinical application. Crit Care Med. 2009 Feb;37(2):713-24. doi: 10.1097/CCM.0b013e3181958d2f.
citation: Bodenstein M, Boehme S, Bierschock S, Vogt A, David M, Markstaller K. Determination of respiratory gas flow by electrical impedance tomography in an animal model of mechanical ventilation. BMC Pulm Med. 2014 Apr 29;14:73. doi: 10.1186/1471-2466-14-73.
citation: Hinz J, Neumann P, Dudykevych T, Andersson LG, Wrigge H, Burchardi H, Hedenstierna G. Regional ventilation by electrical impedance tomography: a comparison with ventilation scintigraphy in pigs. Chest. 2003 Jul;124(1):314-22. doi: 10.1378/chest.124.1.314.
citation: Richard JC, Pouzot C, Gros A, Tourevieille C, Lebars D, Lavenne F, Frerichs I, Guerin C. Electrical impedance tomography compared to positron emission tomography for the measurement of regional lung ventilation: an experimental study. Crit Care. 2009;13(3):R82. doi: 10.1186/cc7900. Epub 2009 May 29.
citation: Victorino JA, Borges JB, Okamoto VN, Matos GF, Tucci MR, Caramez MP, Tanaka H, Sipmann FS, Santos DC, Barbas CS, Carvalho CR, Amato MB. Imbalances in regional lung ventilation: a validation study on electrical impedance tomography. Am J Respir Crit Care Med. 2004 Apr 1;169(7):791-800. doi: 10.1164/rccm.200301-133OC. Epub 2003 Dec 23.