Perioperative Early Tiredness (Acute Fatigue) in Patients With Epithelial Ovarian Cancer

Study Overview
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Brief Summary
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In surgical patients early risk prediction of postoperative complications and organ dysfunctions is still an important clinical challenge whereas appropriate risk predictors are still missing. In this regard, fatigue is a complex phenomenon, is affected by many factors and has been shown to be associated with delayed return to normal activity after surgery. The investigators hypothesize that early tiredness (acute fatigue) assessed shortly after surgery is associated to postoperative complications and organ dysfunctions and might be used for risk stratification. Therefore, in this prospective, observational study the investigators introduce and evaluate a newly developed score to assess early fatigue during the perioperative period (Acute Fatigue Score, AFS). The AFS and the Identity-Consequence Fatigue Scala will be used to assess early fatigue and perioperative time courses and inter-rater-variability will be evaluated. The rating of these two fatigue scores will be evaluated regarding the association with hemodynamic, immunologic, endothelial, metabolic, gastrointestinal measures as well as organ dysfunction and complications after surgery. Furthermore, hemodynamic, immunologic, endothelial, metabolic and gastrointestinal measures are investigated with respect to the intraoperative course and postoperative organ dysfunction and complications. In a subgroup of patients, patients will undergo specialized metabolic measures to investigate mitochondrial dysfunction during the perioperative period.

Official Title
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Association of Perioperative Early Tiredness (Acute Fatigue) With Hemodynamic, Immunologic, Endothelial, Metabolic, Gastrointestinal Measures and Complications in Patients With Epithelial Ovarian Cancer

Conditions
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Perioperative Early Tiredness (Acute Fatigue), Electrical Cardiometry, Biosignals, Mitochondrial Dysfunction, Nutrition

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with epithelial ovarian cancer scheduled for cytoreductive surgery at the Department of Gynecology at Campus Virchow - Klinikum, Charité - University Berlin Offered patient information and written informed consent Exclusion Criteria: Patients aged less than 18 years Persons without the capacity to consent Inability of German language use Lacking willingness to save and hand out data within the study Accommodation in an institution due to an official or judicial order (Unclear) history of alcohol or substances disabuse Coworker of the Charité Known Myopathy Neurological or psychiatric disease at the beginning of hospitalization CHF (congestive heart failure) according to (New York Heart Association) classification - NYHA class IV at the beginning of hospitalization American Society of Anesthesiologists (ASA) classification greater than IV Renal insufficiency (dependency of haemodialysis) at the beginning of hospitalization Pulmonary oedema in thorax x-ray at the beginning of hospitalization History of intracranial hemorrhage within one year before participation in the study Conditions following venous thrombosis within the last three years before study inclusion Known allergies or hypersensitivity on colloidal, starch or gelatine infusion solutions Diabetes mellitus with signs of severe neuropathy Known atrial fibrillation Participation in an interventional clinical trial during the study period; exception: assignment to adjuvant therapy study during this study is allowed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with epithelial ovarian cancer (EOC)<br>Patients undergoing cytoreductive surgery due to epithelial ovarian cancer | |
| Subgroup - Metabolomics in EOC patients without ascites<br>In a subgroup (n=10), patients without preoperative ascites will undergo extended metabolic measures to investigate mitochondrial dysfunction during the preoperative period. | |
| Subgroup - Metabolomics in EOC patients with ascites >500ml<br>In a subgroup (n=10), patients with preoperative ascites >500ml will undergo extended metabolic measures to investigate mitochondrial dysfunction during the preoperative period. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Fatigue Score (AFS) | Rating of the AFS | 1 hour after the end of anaesthesia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Fatigue Score (AFS) | Perioperative time course of the ratings of AFS | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Inter-Rater Variability of Acute Fatigue Score (AFS) | The scores will be assessed by two observers and the variability determined | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Identity-Consequence Fatigue Scala (ICFS) | Previously published score to measure tiredness | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Hemodynamic variables and catecholamine administration | Hemodynamic variables are assessed by the anesthesia monitor | Up to the fifth postoperative day | 
| Hemodynamic variables obtained by Electrical Cardiometry (EC) | EC is a method of bioimpedance | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before, during and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Hemodynamic shock indices calculated from Electrical Cardiometry (EC) | EC is a method of bioimpedance | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before, during and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Heart rate variability, cardiorespiratory coupling, pulse wave velocity and new markers calculated from raw biosignals | Bioelectrical signals to assess the interaction of the cardiac and pulmonary rhythms | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before, during and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Metabolomics/Proteomics | Metabolomic, proteomic, immunological, endothelial and inflammatory markers obtained by intramuscular microdialysis | Up to the first postoperative day | 
| Mitochondrial respiratory chain activities | Respiratory chain activities are assessed in muscle biopsies using high-resolution respirometry | Up to the first postoperative day | 
| Nutrition associated antibodies and deficiency states of vitamins and trace elements | Biochemical parameters of nutrition states and immunological marker of alimentary components are determined | Up to the fifth postoperative day | 
| Blood loss | Perioperative blood loss characteristics | Up to the fifth postoperative day | 
| Body temperature | Body temperature will be assessed continuously and discontinuously | Up to the first postoperative day | 
| Fluid balances | The balances between all orally and intravenously administered fluids and all fluid losses | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before, during and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Blood coagulation markers | Parameters characterizing the humoral and cellular (thrombocytes) coagulation will be determined | Up to the fifth postoperative day | 
| Immunologic, endothelial and hepatic markers | Parameters characterizing the time course of immunological (e.g. Interleukin-6) and endothelial (e.g. Intercellular Adhesion Molecule 1) and hepatic (e.g. cytokeratin-18) response will be determined | Up to the fifth postoperative day | 
| Organ dysfunctions and complications | Organ complications are classified according to Clavien-Dindo classification | Up to the fifth postoperative day, at hospital discharge (an average of two weeks) and before, during and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Microvascular function | Microvascular function is assessed by near-infrared spectroscopy (NIRS) combined with a vascular occlusion test (VOT) | Up to the fifth postoperative day and at hospital discharge (an average of two weeks) | 
| Functional status | Measured by the Barthel activities of daily living (ADL) index and activities of daily living (IADL) | At baseline, hospital discharge (expected average of 14 days) and before and after the first cycle of chemotherapy (an average of four to six weeks) | 
| Intensive care unit length of stay | Time from admission to discharge from the intensive care unit | Participants will be followed up until intensive care unit discharge (an average of two days) | 
| Hospital length of stay | Time from admission to discharge from the hospital | Participants will be followed up until hospital discharge (expected average of 14 days) |