Using the Time of Maximum Effect Site Concentration to Combine Pharmacokinetics and Pharmacodynamics

Minto, Charles F.; Schnider, Thomas W.; Gregg, Keith M.; Henthorn, Thomas K.; Shafer, Steven L.

doi:10.1097/00000542-200308000-00014

Cited by 140 publications

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“…This discrepancy between studies may result from differences in study designs and in criteria for the assessment of intubating conditions. In our study, the induction sequence of anaesthesia took into account the pharmacokinetics ⁄ pharmacodynamics parameters of propofol and remifentanil, so that laryngoscopy and tracheal intubation occured at the effect-site peak concentrations of both agents [21,22].…”

Section: Discussionmentioning

confidence: 99%

Optimal remifentanil dosage for providing excellent intubating conditions when co‐administered with a single standard dose of propofol

et al. 2009

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SummaryThis dose-response study aimed to determine the dose of remifentanil combined with propofol 2.5 mg.kg )1 which provided excellent intubation conditions in 95% of patients. Ninety premedicated female ASA 1 and 2 patients were randomly allocated to five remifentanil dose groups (1, 2, 3, 4 or 5 lg.kg )1 ). Induction of anaesthesia was performed with a blinded dose of remifentanil infused over 60 s simultaneously co-administered with propofol 2.5 mg.kg )1 infused over 45 s. Tracheal intubation was attempted 150 s after the beginning of induction. Intubating conditions were assessed with the Copenhagen score. A probit analysis was performed to calculate the intubating efficient doses (IED) of remifentanil in 95% of patients (IED 95 ). Our data revealed that the IED 95 of remifentanil was 4.0 (95% CI: 3.4-5.6) lg.kg, which was associated with a maximum decrease in heart rate and mean arterial pressure of < 30%, a finding which also applied to the other groups. Excellent intubating conditions are important to minimise the occurrence of damage to the airway, the fourth highest cause of claims related to injuries associated with general anaesthesia [1,2]. The use of neuromuscular blocking drugs at induction of anaesthesia provides significantly better intubating conditions and less vocal cord sequelae than relaxant-free anaesthesia, and has therefore been advocated prior to tracheal intubation for elective surgery [2,3].However, patient factors may contraindicate the use of neuromuscular blocking drugs, and administration of these drugs is associated with several complications, including anaphylactic reactions, residual curarisation, and awareness during general anaesthesia [4][5][6].Significant improvements in the quality of tracheal intubation without paralysis were reported when remifentanil was co-administered with propofol 2 or 2.5 mg.kg )1 [7][8][9][10][11][12][13]. However, the optimal dose of remifentanil required for providing excellent intubating conditions when co-administered with propofol remains unknown since published results are inconsistent [7][8][9][10][11][12][13][14]. This may be related to different protocols with respect to the timing and the speed of infusion of remifentanil and propofol, and the timing and assessment of tracheal intubation.Using an optimised sequence of induction of anaesthesia and a standardised scale for the assessment of the quality of tracheal intubation we therefore conducted a dose-response study to determine the intubating efficient dosage (IED) of remifentanil co-administered with propofol 2.5 mg.kg )1 which would provide excellent intubating conditions in 95% (IED 95 ) of patients undergoing elective surgery. Methods PatientsAfter approval of the study by our institution's Ethics Committee and obtaining patients' written consent, female patients scheduled for elective gynaecological surgery requiring tracheal intubation were enrolled. Inclusion criteria were: ASA 1 and 2 physical status, age from 18 to 65 years and body mass index from 20 to 24 kg.m )2 . Patients ...

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Section: Discussionmentioning

confidence: 99%

Optimal remifentanil dosage for providing excellent intubating conditions when co‐administered with a single standard dose of propofol

et al. 2009

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“…13 This decrease was due to use of a carefully standardized anesthetic induction sequence and consideration of the unique pharmacokinetic and pharmacodynamic attributes of propofol and remifentanil such that LMA insertion occurred at the time when effect-site concentration peaked for both agents. 17,18 In fact, insertion of the LMA constitutes a less noxious stimulus compared with laryngoscopy. Billard et al observed a significant increase in systolic blood pressure ([ 40%) during laryngoscopy and tracheal intubation after induction of anesthesia with propofol 2.5 mgÁkg -1 given alone, 19 whereas Hickey et al 20 reported minor cardiovascular response to insertion of LMA after the same dose of propofol.…”

Section: Discussionmentioning

confidence: 99%

Dose optimale de rémifentanil pour l’insertion d’un masque laryngé lors de la co-administration d’une dose standard unique de propofol

Bouvet

Da-Col

Rimmelé

et al. 2010

Can J Anesth/J Can Anesth

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Purpose This dose-response study aimed to determine the optimal dose of remifentanil combined with propofol 2.5 mgÁkg -1 iv in order to achieve excellent conditions for laryngeal mask airway (LMA TM ) insertion in 95% of adult female patients. Methods Sixty-eight adult premedicated female patients, American Society of Anesthesiologists (ASA) physical status I and II requiring anesthesia for ambulatory surgery, were randomly allocated to one of four remifentanil dose groups (0.25, 0.5, 1, or 2 lgÁkg -1 ). Induction of anesthesia was achieved with one of the four blinded doses of remifentanil infused over 60 sec and simultaneously co-administered with propofol 2.5 mgÁkg -1 iv infused over 45 sec. Insertion of the LMA was attempted 150 sec after the beginning of the induction sequence. Insertion conditions were assessed using a six-category score according to resistance to mouth opening and insertion, swallowing, coughing and gagging, movement, and laryngospasm. A probit analysis was performed to calculate the effective dose for insertion of the LMA in 95% of patients (efficient dose [ED] 95 ). The changes in heart rate (HR) and mean arterial blood pressure (MAP) in response to LMA insertion were recorded and compared as secondary outcome variables. Results The ED 95 of remifentanil was 1.32 (95% confidence interval [CI] 0.99-2.46) lgÁkg -1 . Changes in heart rate and mean arterial pressure were modest and similar over time across groups, with maximum decreases in heart rate and mean arterial pressure \ 30% each during induction of anesthesia. Conclusions The required dose of remifentanil is 1.32 (95% CI 0.99-2.46) lgÁkg -1 to achieve excellent LMA insertion conditions in 95% of patients when co-administered with propofol 2.5 mgÁkg -1 in healthy premedicated female patients undergoing elective ambulatory surgery. RésuméObjectif L'objectif de cette e´tude de dose-re´ponse e´tait de de´terminer la dose optimale de re´mifentanil lors de l'administration conjointe de propofol 2,5 mgÁkg -1 iv afin d'obtenir des conditions excellentes pour l'insertion d'un masque larynge´(LMAÒ) chez 95 % de patientes adultes. Méthode Soixante-huit patientes adultes ASA I et II pre´me´dique´es et ne´cessitant une anesthe´sie pour une chirurgie ambulatoire ont e´te´randomise´es en quatre groupes selon la dose de re´mifentanil (0,25, 0,5, 1 ou 2 lgÁkg -1 ). L'induction de l'anesthe´sie a e´te´re´alise´e avec l'une des quatre doses de re´mifentanil en aveugle perfuse´e sur 60 secondes, administre´e simultane´ment a`du propofol 2,5 mgÁkg -1 iv perfuse´sur 45 secondes. L'insertion du Support was provided solely by institutional sources.

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“…Anaesthesia 2012, 67, [1][2][3][4][5][6][7][8][9][10][11] Editorial data. This is because standard compartmental models are unable to account for differences due to physiology (e.g.…”

Section: Simple Model Structuresmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics – is there anything new?

Rigby-Jones¹,

Sneyd²

2011

Anaesthesia

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Using the Time of Maximum Effect Site Concentration to Combine Pharmacokinetics and Pharmacodynamics

Cited by 140 publications

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Optimal remifentanil dosage for providing excellent intubating conditions when co‐administered with a single standard dose of propofol

Optimal remifentanil dosage for providing excellent intubating conditions when co‐administered with a single standard dose of propofol

Dose optimale de rémifentanil pour l’insertion d’un masque laryngé lors de la co-administration d’une dose standard unique de propofol

Pharmacokinetics and pharmacodynamics – is there anything new?

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