Efficient Trial Design for Eliciting a Pharmacokinetic– Pharmacodynamic Model–based Response Surface Describing the Interaction between Two Intravenous Anesthetic Drugs

Short, Timothy G.; Ho, Tam Yuk; Minto, Charles F.; Schnider, Thomas W.; Shafer, Steven L.

doi:10.1097/00000542-200202000-00027

Cited by 54 publications

(31 citation statements)

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“…When more than one drug is administered to produce an anesthetic effect, as in clinical practice, multiple sigmoid curves can be generated for each concentration of a particular drug. 15,16 Propofol and remifentanil were infused together to produce the measured anesthetic endpoint, which is "response" or "no response" to the stimulus of the procedure. Several pharmacodynamic models were considered to first determine whether there was a significant interaction between the two drugs; subsequently, models were considered that would best characterize the interaction between the two drugs.…”

Section: Deriving the Interaction From The Study Datamentioning

confidence: 99%

Determination of the Pharmacodynamic Interaction of Propofol and Remifentanil during Esophagogastroduodenoscopy in Children

et al. 2004

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Section: Deriving the Interaction From The Study Datamentioning

confidence: 99%

Determination of the Pharmacodynamic Interaction of Propofol and Remifentanil during Esophagogastroduodenoscopy in Children

et al. 2004

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“…The study was originally designed and powered to develop a propofol-remifentanil pharmacodynamic model and 24 volunteers were chosen because Short et al 15 had shown that 20 subjects would be required to define a model surface adequately using a crisscross study design for assessing drug interaction. The ethics approval was to collect the original volunteer data.…”

Section: Volunteer Recruitment and Instrumentationmentioning

confidence: 99%

Using the Entropy of Tracheal Sounds to Detect Apnea during Sedation in Healthy Nonobese Volunteers

Ting

Hill

et al. 2013

Anesthesiology

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Background: Undetected apnea can lead to severe hypoxia, bradycardia, and cardiac arrest. Tracheal sounds entropy has been proved to be a robust method for estimating respiratory flow, thus maybe a more reliable way to detect obstructive and central apnea during sedation. Methods: A secondary analysis of a previous pharmacodynamics study was conducted. Twenty volunteers received propofol and remifentinal until they became unresponsive to the insertion of a bougie into the esophagus. Respiratory flow rate and tracheal sounds were recorded using a pneumotachometer and a microphone. The logarithm of the tracheal sound Shannon entropy (Log-E) was calculated to estimate flow rate. An adaptive Log-E threshold was used to distinguish between the presence of normal breath and apnea. Apnea detected from tracheal sounds was compared to the apnea detected from respiratory flow rate. Results: The volunteers stopped breathing for 15 s or longer (apnea) 322 times during the 12.9-h study. Apnea was correctly detected 310 times from both the tracheal sounds and the respiratory flow. Periods of apnea were not detected by the tracheal sounds 12 times. The absence of tracheal sounds was falsely detected as apnea 89 times. Normal breathing was detected correctly 1,196 times. The acoustic method detected obstructive and central apnea in sedated volunteers with 95% sensitivity and 92% specificity. Conclusions: We found that the entropy of the acoustic signal from a microphone placed over the trachea may reliably provide an early warning of the onset of obstructive and central apnea in volunteers under sedation. UNdETEcTEd apnea can lead to severe hypoxia, bradycardia, and even cardiac arrest.1 Pulse oximetry and capnography are recommended by the American Society of Anesthesiologists for monitoring spontaneous breathing in patients receiving moderate sedation.2 A pulse oximeter detects hypoxemia by continuously measuring the oxygen saturation of arterial blood so that apnea can be discovered, but there can be significant delay between the onset of apnea and oxygen desaturation, especially when the patient receives supplemental oxygen or when hypothermia and vasoconstriction are present.3-5 capnography detects apnea by the absence of carbon dioxide in expired gas, but reliably sampling exhaled gas with a face mask or nasal cannula is problematic in nonintubated patients. 6,7 Tracheal sounds originate from the vibrations of the tracheal wall and surrounding soft tissues caused by gas pressure fluctuations in the trachea. 8 The signals from a microphone or a piezo-electric film transducer placed over the trachea have been processed to monitor respiratory rate Received from the Department of Biomedical Engineering, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, P. R. China, and the Department of Anesthesiology, University of Utah, Salt Lake City, Utah. Submitted for publication April 10, 2012. Accepted for publication January 18, 2013. Supported by a grant from China Medical University, Shenyang,...

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“…Dosing Regimen. The study design was a modification of the criss-cross design proposed by Short et al 3 The choice of the sevoflurane/remifentanil concentrations pairs were based on the sevoflurane Ce50 (Ce50 sevo ) to suppress the response to skin incision (ϭ minimal anesthetic concentration, MAC) of 1.85% 13 and a remifentanil Ce50 (ϭ remifentanil concentration reducing the MAC SEVO by 50%) of 1.5 ng/ml 14 :…”

Section: Drug Administrationmentioning

confidence: 99%

“…1,2 Using the mathematically defined response surface, the corresponding drug effect for any two or more drug concentrations of the interacting drugs can be predicted. 1,3 Various methodological approaches to response surface models are found in the literature. Bol et al further developed a previously published response surface model by Greco et al to describe the interaction between dexmedetomidine and midazolam in rats.…”

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confidence: 99%

Sevoflurane Remifentanil Interaction

et al. 2012

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Background: Various pharmacodynamic response surface models have been developed to quantitatively describe the relationship between two or more drug concentrations with their combined clinical effect. We examined the interaction of remifentanil and sevoflurane on the probability of tolerance to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy in patients to compare the performance of five different response surface models. Methods: Forty patients preoperatively received different combined concentrations of remifentanil (0 -12 ng/ml) and sevoflurane (0.5-3.5 vol.%) according to a criss-cross design (160 concentration pairs, four per patient). After having

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Efficient Trial Design for Eliciting a Pharmacokinetic– Pharmacodynamic Model–based Response Surface Describing the Interaction between Two Intravenous Anesthetic Drugs

Abstract: The results showed that a number of trial designs would be viable, but a design that crossed the surface in a crisscross fashion would give the most robust result with the least patients.

Cited by 54 publications

References 1 publication

Determination of the Pharmacodynamic Interaction of Propofol and Remifentanil during Esophagogastroduodenoscopy in Children

Determination of the Pharmacodynamic Interaction of Propofol and Remifentanil during Esophagogastroduodenoscopy in Children

Using the Entropy of Tracheal Sounds to Detect Apnea during Sedation in Healthy Nonobese Volunteers

Sevoflurane Remifentanil Interaction

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