Investigation of Oxidative Stress in Appendectomy - Open Versus Laparoscopic in Childhood and Adolescence

Appendicitis Acute Clinical Trial

— OSAE  

Official title:

Investigation of Oxidative Stress - Open Appendectomy (OAE) Versus Laparoscopic Appendectomy (LAE) in Childhood and Adolescence - A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03723642
• Other study ID #: 30-120 ex 17/18
• Status: Recruiting
• Phase: N/A
• Start date: October 2, 2019
• Est. completion date: December 1, 2020

Study information

• Verified date: July 2020
• Source: Medical University of Graz
• Contact: Gert Warncke, MD
• Phone: 01143316385
• Email: gert.warncke[@]medunigraz.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In the planned prospective randomized study, oxidative stress will be investigated by analyzing volatile organic compounds in the exhaled air in children. Children who have undergone open versus laparoscopic surgery for appendicitis will be compared. A better understanding of the effects of the surgical technique could be a prerequisite for an optimized surgical setting. It could also lead to recommendations for pre- or perioperatively antioxidative agents.

Description:

Aim of the study: In the planned prospective randomized study, oxidative stress will be investigated by analyzing VOCs (volatile organic compounds) in the exhaled breath in children undergoing open or laparoscopic surgery for appendicitis at the Department of Pediatric and Adolescent Surgery of the Medical University of Graz. A resulting better understanding of the effects of the surgical technique can a) be a pre-condition for an optimized surgical setting and b) possibly lead to recommendations of pre- or perioperatively antioxidatively active substances and c) be a base for future surgical procedures.

Study design: This is a prospective randomized pilot study in children and adolescents undergoing surgery due to acute appendicitis. Patients with complicated appendicitis and those with an intraoperatively caused disorder will be excluded. The operation within the context of this study is exclusively conducted by specialists of the Department of Pediatric and Adolescent Surgery of the Medical University of Graz, who perform both - open and laparoscopic surgical techniques. 40 patients aged 6-18 years suffering from acute appendicitis are to be included. These are divided into 2 groups. Group 1 (n = 20) with laparoscopic and group 2 (n = 20) with open appendectomy.

Recruitment and compensation of study participants: Parents/patients are made aware of the study by means of an information sheet and are provided with a declaration of consent if interested. Participants do not receive any compensation for participating in the study.

Sampling of exhaled VOCs (volatile organic compounds) using NTME (needle trap microextraction) for measurement OS (oxidative stress): Number of samples: 2 samples each from exhaled breath at the times defined below (in total n = 12). The time of sampling: t1 before anaesthetic introduction (n = 2); t2 after anesthetic introduction (n = 2); t3 15 minutes after cut (n = 2); t4 30 minutes after cut (n = 2); t5 45 minutes after cut (n = 2); t6 after seam (n = 2).

Analysis of exhaled VOCs for measurement OS: The exhaled breath samples taken are placed in an injector of a gas chromatograph into the inert carrier gas stream (He). The substances are assigned according to their retention time in the chromatogram and its mass spectrum. Unknown connections in the mass spectrum of exhaled breath is used as a basis for comparison with a reference database.

Sampling of blood markers for measurement OS: a) sampling times for WBCs, CRP: t1 = 1 sample preoperatively (before anaesthetic introduction) and t2 = 1 sample after 24 h. b) sampling times for malondialdehyde: t1 = 1 sample before anaesthetic introduction and t2 = 1 sample after suture.

Histopathological grading: The explanted vermiform appendix becomes the histopathological Refurbishment at the Institute of Pathology of the Medical University of Graz. There the classification is made according to the histopathological findings in 4 degrees of severity (acute focal appendicitis, acute suppurative appendicitis, acut gangrenous appendicitis, perforated appendicitis).

Sampling WBCs, CRP: These are carried out within the scope of routine diagnostics due to the clinical presentation of the AA (acute appendicitis).

Sampling VOCs: 2 breath samples are taken from each patient during expiration, taken from it. To collect the samples, the investigators use an automatic Sampling device connected directly to a capnometer. This system works with microextraction (NTME) and enables a automatic sampling of the alveolar air, i.e. in the plateau of the CO2 curve. The samples are sent to the Intitute of Rostock Medical Breath Analysis and Technologies (RoMBAT) as cooperation partner. This partner was selected because it already has extensive experience with the methodology and studies on oxidative stress during operations.

Malondialdehyde (MDA) sampling: Malondialdehyde is analysed at the Clinical Institute for Medical and Chemical Laboratory Diagnostics at the Medical University of Graz means of ultra-modern GC-MS method. For this purpose, the patient is assigned to the two Measuring times 2 x 400 μl EDTA plasma taken. The second sample serves only as a safety measure if repeat measurements are necessary. The samples obtained must be deep-frozen at -80 °C within 2 hours. . Subsequently (at the latest on the following day) the samples must be analyzed to the Institute.

Planned evaluation: The statistical investigations are carried out with SPSS 23.0®. Graphical representation of the data is performed with GraphPad Prism 7®. To investigate whether the main target variables (VOCs) differ in the course between the two groups, linear models are used for repeated measurements with group (open versus laparoscopic appendectomy) as intermediate subject factor and time of measurement (t1 to t6) as internal subject factor. In the case of deviations from the normal distribution, transformations are taken into consideration. The secondary targets, i.e. the changes in the serum markers on theTimes t1 and t6, are compared between the 2 groups (open versus laparoscopic appendectomy) by Mann-Whitney U-test (data not normally distributed) or independent T-test (with normal distribution). In order to establish relationships between the VOCs and the serum markers for oxidative stress at times t1 and t6 a correlation analysis is performed (depending on the data, Pearson or Spearman Rho). All statistical tests are carried out on two sides and all p-values are interpreted purely exploratively.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 1, 2020
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria:

• Age from 6-18 years

• reliable diagnosis of acute appendicitis

• surgical therapy using open/laparoscopic surgical technique

• given approval

Exclusion Criteria:

• Age not between 6 and 18 years

• chronic underlying disease/autoimmune disease

• complicated appendicitis (perforation, consecutive purulent peritonitis, abscess formation)

• infection outside acute appendicitis

• SIRS

• taking medications containing the cytochrome P450 (CYP) system affect including cortisone

• impaired liver function

• unaccepted consent

Related Conditions & MeSH terms

• Appendicitis
• Appendicitis Acute

Intervention

Diagnostic Test:
• Initial serum malondialdehyde level
Blood sample (0.4ml) will be obtained within 5 minutes before induction of general anaesthesia. Samples will be obtained in both groups (LAE and OAE)
• Final serum malondialdehyde level
Blood sample (0.4ml) will be obtained within 5 minutes after wound closure. Samples will be obtained in both groups (LAE and OAE)
• Initial differential white blood cell count
Differential blood counts (microscopic) will be obtained during pre-operative routine work-up. Samples will be obtained in both groups (LAE and OAE).
• Final differential white blood cell count
Differential blood counts (microscopic) will be obtained 24h after the first sample (Initial differential blood count). Samples will be obtained in both groups (LAE and OAE).
• Initial c-reactive protein serum level
C-reactive protein levels will be obtained during pre-operative routine work-up. Samples will be obtained in both groups (LAE and OAE).
• Final c-reactive protein serum level
C-reactive protein levels will be obtained 24h after the first sample (initial c-reactive protein level). Samples will be obtained in both groups (LAE and OAE).
• Initial VOC
Volatile organic compound sampling (2 samples within 5 minutes) within 10 minutes before induction of general anesthesia
• VOC 5min
Volatile organic compound sampling (2 samples within5 minutes) within 5 minutes after endotracheal intubation before skin incision.
• VOC 15min
Volatile organic compound sampling (2 samples within 5 minutes) 15 minutes after skin incision.
• VOC 30min
Volatile organic compound sampling (2 samples within 5 minutes) 30 minutes after skin incision.
• VOC 45min
Volatile organic compound sampling (2 samples within 5 minutes) 45 minutes after skin incision.
• Final VOC
Volatile organic compound sampling (2 samples within 5 minutes) within 5 minutes after skin closure.

Locations

Country	Name	City	State
Austria	Department of Paediatric and Adolescent Surgery	Graz

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Graz	Graz University of Technology, University of Rostock

Country where clinical trial is conducted

Austria, 

References & Publications (27)

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Are volatile respiratory gas markers for oxidative stress (such as pentanes, isoprenes) dependent on the surgical method (open versus laparoscopic appendectomy)?	We investigate the respiratory volatile organic compounds before, during and at the end of surgery and compare the respiratory gas profiles of the two groups open versus laparoscopic appendectomy.	1 year
Secondary	Alterations of serum malondialdehyde serum levels.	The changes of the serum marker for oxidative stress MDH before and after surgery will be investigated and the changes in open versus laparoscopic appendectomy will be compared. One sample will be taken preoperatively and one sample postoperatively.	1 year
Secondary	Alterations of inflammation markers.	The changes of the serum inflammation markers before and after surgery will be investigated and the changes in open versus laparoscopic appendectomy will be compared.	1 year