Bispectral Index Guided Sevoflurane Titration

Study Overview
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Brief Summary
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Electroencephalographic-based monitoring systems such as the bispectral index (BIS) may reduce anaesthetic overdose rates. The investigators hypothesised that goal-directed sevoflurane administration (guided by BIS monitoring) could reduce the sevoflurane plasma concentration (SPC) and intraoperative vasopressor doses during on-pump cardiac surgery in a prospective, controlled, sequential two-arm clinical study.

Detailed Description
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Electroencephalographic (EEG)-based monitoring systems, for example the bispectral index [(BIS); BIS monitor, Covidien, Boulder, Colorado, USA], were designed to prevent anaesthesia underdosage with the risk of awareness and to reduce the time to awakening after terminating general anaesthesia. However, little is known about the consequences of anaesthetic overdose. The investigators assume that high doses of anaesthetics result in cardiocirculatory depression and the necessity for high-dose vasopressor therapy, followed by microcirculation disorder and organ dysfunction. The investigators hypothesised that in on-pump cardiac-surgery, goaldirected administration of sevoflurane guided by BIS monitoring reduces excessive sevoflurane plasma concentration (SPC) and the need for an intraoperative vasopressor. To test this hypothesis, the current study compared BIS-guided sevoflurane administration with the constant delivery of an inspired sevoflurane concentration of 1.8% during on-pump cardiac surgery and analysed its effect on the SPC and the required intraoperative dosage of norepinephrine. The study population was divided into two patient groups: Thirty-three on-pump cardiac surgery patients enrolled in the study were allocated to a conventionally treated control group, with the constant administration of an inspired concentration of sevoflurane 1.8% (group Sevo1.8%). Thirty-four patients were sequentially allocated to an interventional group with BIS-guided administration of sevoflurane (group SevoBIS). Vasoactive drugs were administered according to the following protocol in both groups. If the mean arterial blood pressure decreased below 50 mmHg, a continuous infusion of norepinephrine was given to maintain a perfusion pressure between 50 and 60 mmHg during cardiopulmonary bypass. If the mean arterial pressure increased above 75 mmHg, nitroglycerine was used in boluses of 0.1 mg until arterial pressure returned to a mean of less than 75 mmHg. If mean arterial pressure persisted above 75 mmHg after a cumulative administration of nitroglycerine 1.0 mg, urapidil was administered in boluses of 0.1 mg/kg until the perfusion pressure decreased below 75 mmHg. At the end of the surgical procedure, all patients were transferred to the ICU.

Official Title
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Bispectral Index Guided Titration of Sevoflurane in On-pump Cardiac Surgery Reduces Plasma Sevoflurane Concentration and Vasopressor Requirements

Conditions
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Intraoperative Hypotension

Intervention / Treatment
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* Device: Bispectral index Monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing elective on-pump cardiac surgery and an American Society of Anesthesiologists' (ASA) physical status of 3 to 4 Exclusion Criteria: A contraindication to the administration of volatile anaesthetics, an active infection with a temperature more than 38°C and any history of neurological disease

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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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group Sevo1.8%<br>Anaesthesia was maintained with a constant inspired concentration of sevoflurane 1.8% (Sevorane; Abbvie, Wiesbaden, Germany) administered via the ventilator. From the beginning of CPB, a constant flow of sevoflurane 1.8% was administered with the oxygenator fresh-gas supply, using a common anaesthetic vaporiser (Draeger Vapor Version 2000; Draeger, Luebeck, Germany). Following successful weaning from CPB, sevoflurane was again administered at an inspired concentration of 1.8% using the ventilator. | |
| Experimental: Bispectral index Monitoring<br>The sevoflurane concentration via the ventilator and the oxygenator fresh gas supply was titrated to maintain a target BIS value between 40 and 60 (BIS-Monitor, Covidien, Boulder, Colorado, USA). However, the concentration of sevoflurane in the oxygenator fresh gas supply was not reduced below 0.3%. | Device: Bispectral index Monitoring<br>* In group SevoBIS, the sevoflurane concentration was titrated to maintain a target BIS value between 40 and 60.<br>* Other names: BIS-Monitor, Covidien, Boulder, Colorado, USA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative intraoperative administration of norepinephrine |  | During operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sevoflurane concentration in the oxygenator freshgas supply during cardiopulmonary bypass |  | During operation | 
| Postoperative blood lactate concentration |  | Upon arrival in the intensive care unit (ICU) | 
| Duration of postoperative mechanical ventilation |  | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 
| ICU length of stay |  | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 
| Incidence of acute kidney injury |  | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 
| Sevoflurane Plasma Concentration during CPB |  | During operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anaesthetics inhalation, Bispectral index, Cardiopulmonary bypass