Pharmacotherapy Personalization of Cancer Patients

Study Overview
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Brief Summary
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Treatment personalization could ensure better outcome than standard procedures. It is particularly important in intensive care units where patients received many drugs and procedures. Their health status can change very fast. The oncologic patients treated in intensive care units are a special group of patients. Factors related to cancer influence extra their health status. The aim of this study is population pharmacokinetic-pharmacodynamic analysis drugs that are routinely used during an analgosedation in ICU oncologic patients. Analgosedation is monitored by drugs plasma concentration, the depth of sedation (bispectral index) and vital parameters like: systolic and diastolic blood pressure, mean arterial pressure, heart rate. Moreover, the TNM Staging System, biochemical parameters, The American Society of Anesthesiologists (ASA) physical status classification will be checked like potential factors influencing on pharmacokinetics and pharmacodynamics drugs used in the study.

Detailed Description
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The oncologic patients are qualified to head and neck tumor resection in general anesthesia. The anesthesia introduction is performed with single dose of midazolam, fentanyl, rocuronium and propofol/etomidate. Sevoflurane is used in anesthesia maintenance. Patients are transported to ICU after operation. Then they are kept for several hours in analgosedation. All used drugs are given by intravenous continuous infusion. Oxycodone is an analgesic component of analgosedation. Midazolam, dexmedetomidine and/or propofol are used as sedatives (2-3 drugs in every patient). Whole blood samples (2.0 ml) are collected during the study to measure drugs concentrations - 3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation. Vital parameters and bispectral index are monitored during analgosedation and 6 hours after the infusion cessation and noted every 15-60 minutes.

Official Title
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Pharmacotherapy Personalization of Cancer Patients Based on Modern Analytical and Computational Techniques

Conditions
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Head and Neck Neoplasms, Oncologic Patients

Intervention / Treatment
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* Drug: Infusion Intravenous


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age over 18 years old, qualifications to oncologic surgery, needing of analgosedation in ICU after an operation Exclusion Criteria: proven allergies to used in anesthetics or/analgosedation medicaments, lack of written confirmed consent of a patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Analgosedation in ICU patients after head and neck tumor resection in general anesthesia<br>Head and neck tumor resections were performed in general anesthesia. Midazolam and etomidate or propofol were used in introduction and then anesthesia was maintenance with sevoflurane. Patients received intravenous continuous infusion of oxycodone as an analgesic component and sedatives (propofol/dexmedetomidine/midazolam) during analgosedation in ICU. | Drug: Infusion Intravenous<br> <br> * Other names: Analgesics and sedatives intravenous continuous infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the depth of sedation using bispectral index | Continuous measurement of the depth of sedation using bispectral index during analgosedation in intensive care unit. | from the beginning of analgosedation to 6 hours after analgosedation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxycodone plasma concentrations [ng/ml] | Measurements of oxycodone and noroxycodone plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol. | 3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation | 
| Dexmedetomidine plasma concentrations [ng/ml] | Measurements of dexmedetomidine plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol. | 3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation | 
| Midazolam plasma concentrations [ng/ml] | Measurements of midazolam and alfa-hydroxymidazolam plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol. | 3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation | 
| Propofol plasma concentrations [ng/ml] | Measurements of propofol plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol. | 3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation | 
| Systolic blood pressure | Measurements of systolic blood pressure during analgosedation in intensive care unit. | before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation | 
| Diastolic blood pressure | Measurements of diastolic blood pressure during analgosedation in intensive care unit. | before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation | 
| Heart rate | Measurements of heart rate during analgosedation in intensive care unit. | before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation | 
| Mean arterial pressure | Measurements of mean arterial pressure during analgosedation in intensive care unit. | before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, Intensive Care Units, Pharmacokinetics, Pharmacodynamics, Surgical patients, Analgosedation