Modeling and Application of Triple Drug Response Surface Models

Summary

Demand for anesthesiologists outside the operating rooms is increasing. Surgeons, radiologists, endoscopists and other interventionists are performing procedures with greater complexity, sometimes accompanied by greater pain and therefore require some sedation. This growing need place a pivotal role on careful handling the delivered drugs. Specifically, the investigators wish to know how different classes of drugs interact in order for us to titrate the effects more precisely. Early studies used isobolograms and concentration effect curves as their tools but these methods are limited and incapable of making continuous bedside monitoring. Researchers integrated these methodologies mathematically and developed response surface models. It's becoming a very convenient tool to assess drug interactions. Drug interactions are visualized with a three dimensional graph, or a surface. Users will only need the calculated drug concentrations and a predicted loss of response probability will be given after a model is built. The process of model construction is complex and time demanding process. Our team has successfully built a dual-drug model for midazolam and alfentanil and several works have been published in renowned anesthesia journals. Dual-drug models are simple but their use is very limited. The investigators often use more than two drugs during practice and a three-drug model will be a great leap to monitor clinical pharmacodynamics. The investigators will collect vital signs, anesthestic depth (BIS=bispectral index, analgesia nociception index (ANI)), drug dosing (propofol, midazolam and alfentanil), and the MOAA/S (modified observer's assessment/alertness score) scores in patient who are receive routine general anesthesia under laryngeal mask or sedation for TEE (transesophageal echocardiography) examinations. Patient's consent will be obtained prior to enrollment. These recordings will be pooled into computer program for model construction. A novel model in the field of anesthesia was chosen and modified. As pioneers in this field in Taiwan, the investigators plan to perform a series of analysis using a novel model the investigators have built to look into detail on how drugs interact with each other. A safety boundary to avoid excessive respiratory depression can be drawn by the model. The main goal is to provide sedation that gives precision, patient comfort, rapid return of consciousness and safety based on the triple-drug response surface model.

Conditions

• Pharmacodynamics
• Drug Interactions

Interventions

DRUG

Fentanyl

The investigators assess the depth of anesthesia based on bispectral index (BIS) and modified observer's assessment/alertness scale (MOAA/S) after routine drug regimen is given. BIS is maintained between 40 and 60 and MOAA/S less than 1. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Typical fentanyl ranged from 0\~200mcg according to patient condition. The timing and doses are recorded for backend analysis. At the conclusion of the surgery, the patient is observed in the operation room until return of consciousness before sending them to the recovery unit.

OTHER

Bispectral index (BIS) and analgesia nociception index (ANI)

After giving routine anesthetic medications, the investigators assess the depth of anesthesia based on bispectral index (BIS) and modified observer's assessment/alertness scale (MOAA/S). BIS is maintained between 40 - 60 and MOAA/S less than 2. The vital signs, BIS, analgesia nociception index (ANI) are recorded automatically and continuously through computerized software. ANI is used to observational purposes only and do not guide anesthetic management in our protocol. Upon conclusion of the surgery or examination, the patient is observed until return of consciousness (MOAA/S = 5) before sending them to the recovery unit.

DRUG

alfentanil

The investigators assess the depth of anesthesia based on bispectral index (BIS) and modified observer's assessment/alertness scale (MOAA/S) after routine drug regimen is given. BIS is maintained between 40 and 60 and MOAA/S less than 2. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Typical alfentanil ranged from 0\~1000mcg according to patient condition. The timing and doses are recorded for backend analysis. At the conclusion of the examination, the patient is observed in the examination room until return of consciousness before sending them to the recovery unit.

DRUG

Propofol

The investigators assess the depth of anesthesia based on bispectral index (BIS) and modified observer's assessment/alertness scale (MOAA/S) after routine drug regimen is given. BIS is maintained between 40 and 60 and MOAA/S less than 2. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Typical propofol ranged from 0\~200mg according to patient condition. The timing and doses are recorded for backend analysis. At the conclusion of the surgery or examination, the patient is observed in the surgery or examination room until return of consciousness before sending them to the recovery unit.

DRUG

sevoflurane

The investigators assess the depth of anesthesia based on bispectral index (BIS) and modified observer's assessment/alertness scale (MOAA/S) after routine triple drug regimen is given. BIS is maintained between 40 and 60 and MOAA/S less than 1. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Typical sevoflurane concentration ranged from 0\~3% according to patient condition. The timing and concentrations data are acquired for backend analysis. At the conclusion of the surgery, the patient is observed in the surgery room until return of consciousness before sending them to the recovery unit.

DRUG

midazolam

The investigators assess the depth of anesthesia based on bispectral index (BIS) and modified observer's assessment/alertness scale (MOAA/S) after routine drug regimen is given. BIS is maintained between 40 and 60 and MOAA/S less than 2. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Typical midazolam ranged from 0\~5mg in boluses according to patient condition. The timing and doses are recorded for backend analysis. At the conclusion of the examination, the patient is observed in the examination room until return of consciousness before sending them to the recovery unit.

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan

  lead OTHER_GOV

Principal Investigators

• Jing Yang Liou, MD · Taipei Veterans General Hospital; National Yang-Ming University

Eligibility

Min Age

20 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-06-12

Primary Completion

2022-05-01

Completion

2022-05-25

FDA Drug

Yes

FDA Device

Yes

Countries

• Taiwan

Study Locations