Effect of Propofol Midazolam on Cerebral Oxygenation and Metabolism During Clipping of Ruptured Cerebral Aneurysm

Study Overview
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Brief Summary
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Despite the theoretical benefits of i.v. agents, volatile agents remain popular. In a study comparing desflurane, isoflurane, and sevoflurane in a porcine model of intracranial hypertension, at equipotent doses and normocapnia, cerebral blood flow (CBF) and ICP were least with sevoflurane. Propofol is the most commonly used intravenous anesthetic. It has many theoretical advantages by reducing cerebral blood volume (CBV) and ICP and preserving both autoregulation and vascular reactivity. Neurosurgical patients anaesthetized with propofol were found to have lower ICP and higher CPP than those anaesthetized with isoflurane or sevoflurane. The well known pharmacodynamic advantages of intravenous anesthetics may give this group of drugs superior cerebral effects when compared with inhalation anesthetics.

Detailed Description
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The aim of this study is to evaluate the cerebral hemodynamics and global cerebral oxygenation as well as the systemic hemodynamic changes using midazolam and propofol as total intravenous anesthetics (TIVA) in comparison with sevoflurane anesthesia in clipping of ruptured cerebral aneurysm.

Official Title
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Cerebral Oxygenation and Metabolism in Patients Undergoing Clipping of Cerebral Aneurysm: A Comparative Study Between Propofol-based Total Intravenous Anesthesia and Sevoflurane-based Inhalational Anesthesia

Conditions
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Ruptured Cerebral Aneurysm

Intervention / Treatment
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* Drug: Total intravenous anesthesia (TIVA)
* Drug: Inhalation Anesthesia
* Drug: Rescue fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists physical status III or IV. Exclusion Criteria: Morbid obese patients. Severe or uncompensated cardiovascular diseases Severe or decompensated renal diseases Severe or decompensated hepatic diseases Severe or decompensated endocrinal diseases. Pregnancy Postpartum Lactating females Allergy to one of the agents used. Severely altered consciousness level. Sitting or prone position during surgery.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total intravenous anesthesia (TIVA)<br>Patients will receive total intravenous anesthesia using Propofol and Midazolam | Drug: Total intravenous anesthesia (TIVA)<br>* Propofol (1.5-2 mg/kg/h) infusion, Midazolam (0.12 mg/kg/h) infusion<br>Drug: Rescue fentanyl<br>* Fentanyl in repeated doses (50 µg) when needed (heart rate or mean arterial blood pressure increase more than 20% of the basal value) are used for maintenance of analgesia<br>|
| Active Comparator: Inhalation Anesthesia<br>Patients will receive Inhalation anesthesia using Sevoflurane | Drug: Inhalation Anesthesia<br>* Sevoflurane at a concentration of 2-2.5%<br>Drug: Rescue fentanyl<br>* Fentanyl in repeated doses (50 µg) when needed (heart rate or mean arterial blood pressure increase more than 20% of the basal value) are used for maintenance of analgesia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterio-Jugular oxygen content difference | The differences between arterial and jugular bulb oxygen contents | Immediately before and every 30 min for 6 hour following start of surgery | 
| Estimated cerebral metabolic rate for O2 (eCMRO2) | eCMRO2=Ca- jO2 x(PaCO2 ∕ 100), Where Ca jO2 is arterio-jugular O2 content difference. PaCO2 is arterial CO2 tension | Immediately before and every 30 min for 6 hour following start of surgery | 
| Cerebral Extraction Rate of O2 (CEO2) | Calculated as the differences between arterial and jugular bulb O2 saturations, CEO2 = SaO2 - SjvO2 | Immediately before and every 30 min for 6 hour following start of surgery | 
| Cerebral Blood Flow equivalent (CBFe) | : Which is an index of flow metabolism relationship, calculated as a reciprocal of arterio-jugular O2 content difference. CBFe = 1 ∕CaO2-CjvO. | Immediately before and every 30 min for 6 hour following start of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate |  | Immediately before and every 30 min for 6 hour following start of surgery | 
| Mean arterial blood pressure |  | Immediately before and every 30 min for 6 hour following start of surgery | 
| Peripheral oxygen saturation |  | Immediately before and every 30 min for 6 hour following start of surgery | 
| Central venous pressure |  | Immediately before and every 30 min for 6 hour following start of surgery | 
| End tidal carbon dioxide tension |  | Immediately before and every 30 min for 6 hour following start of surgery | 
| Sedation score | - Postoperative level of sedation of all patients will be evaluated using Ramsay sedation scale | For 6 hours from induction of anesthesia | 
| Time for first analgesic request from extubation | Time for first analgesic request from extubation | For 6 hours from induction of anesthesia | 
| Duration of stay in intensive care unit |  | For 5 days after surgery |