Propofol Dosing Regimens for ICU Sedation Based upon an Integrated Pharmacokinetic– Pharmacodynamic Model

Barr, Juliana; Egan, Talmage D.; Sandoval, Nancy F.; Zomorodi, Katayoun; Cohane, Carol; Gambús, Pedro L.; Shafer, Steven L.

doi:10.1097/00000542-200108000-00011

Cited by 144 publications

(88 citation statements)

References 21 publications

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“…Although, a longer extubation time would have predicted with dexmedetomidine from volunteer pharmacokinetic data [14], as the elimination half-life of propofol [15] is approximately three times shorter (30-60 min for propofol vs 100-150 min) for dexmedetomidine. In our study similar extubation time may be due to the less dose of fentanyl in dexmedetomidine group.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Dexmedetomidine, Propofol and Midazolam for Short-Term Sedation in Postoperatively Mechanically Ventilated Neurosurgical Patients

Srivastava¹

2014

JCDR

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Section: Discussionmentioning

confidence: 99%

Comparison of Dexmedetomidine, Propofol and Midazolam for Short-Term Sedation in Postoperatively Mechanically Ventilated Neurosurgical Patients

Srivastava¹

2014

JCDR

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“…Barr et al 33 correlated propofol concentrations to sedation scores, but in mechanically ventilated patients in the intensive care unit. The values of C 50 reported were 0.13, 0.5, 0.74, 1.48, and 2.34 g/ml for Ramsay sedation scores of 2, 3, 4, 5, and 6, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Opioids can increase the sedative properties of propofol or alter its pharmacokinetics. Integrating results from the pharmacokinetic and pharmacodynamic analyses, Barr et al 33 were able to develop dosing regimens for propofol in patients in the intensive care unit and described interesting features such as the emergence time (i.e., time required for the level of sedation to decrease from 5 to 2). This type of information could not be extracted from our results since no kinetic model was proposed; therefore, the pharmacokinetics of propofol in patients with PD with nonconcomitant administration of opioids should be specifically addressed.…”

Section: Discussionmentioning

confidence: 99%

Modeling of the Sedative and Airway Obstruction Effects of Propofol in Patients with Parkinson Disease undergoing Stereotactic Surgery

Fàbregas

Rapado²,

Gambús

et al. 2002

Anesthesiology

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Background: Functional stereotactic surgery requires careful titration of sedation since patients with Parkinson disease need to be rapidly awakened for testing. This study reports a population pharmacodynamic model of propofol sedation and airway obstruction in the Parkinson disease population.Methods: Twenty-one patients with advanced Parkinson disease undergoing functional stereotactic surgery were included in the study and received propofol via target-controlled infusion to achieve an initial steady state concentration of 1 g/ml. Sedation was measured using the Ramsay Sedation Scale. Airway obstruction was measured using a four-category score. Blood samples were drawn for propofol measurement. Individual pharmacokinetic profiles were constructed nonparametrically using linear interpolation. Time course of sedation and respiratory effects were described with population pharmacodynamic models using NONMEM. The probability (P) of a given level of sedation or airway obstruction was related to the estimated effect-site concentration of propofol (Ce) using a logistic regression model. Results:The concentrations predicted by the target-controlled infusion system generally exceeded the measured concentrations. The estimates of C 50 for Ramsay scores 3, 4, and 5 were 0.1, 1.02, and 2.28 g/ml, respectively. For airway obstruction scores 2 and 3, the estimates of C 50 were 0.32 and 2.98 g/ml, respectively. Estimates of k e0 were 0.24 and 0.5 1/min for the sedation and respiratory effects, respectively.Conclusions: The pharmacokinetic behavior of propofol in patients with Parkinson disease differs with respect to the population from which the model used by the target-controlled infusion device was developed. Based on the results from the final models, a typical steady state plasma propofol concentration of 0.35 g/ml eliciting a sedation score of 3 with only minimal, if any, airway obstruction has been defined as the therapeutic target.

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“…Current guidelines for maximal propofol dosage suggested < 4 mg/kg//h for a duration of up to 48 h [22]. Recently, fatal cases of PIS at low infusion rates (1.9 -5.1 mg/ kg/h) have been reported [23].…”

Section: Propofol Infusion Syndrome (Pis)mentioning

confidence: 99%

Terlipressine Induced Rhabdomyolysis After Orthotopic Liver Transplantation

Eĭd

2014

J Med Cases

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In this report we present a fatal case of severe rhabdomyolysis during early recovery following a complicated but successful orthotopic liver transplantation. The key point in this case is skin necrosis and we consider that the clinical association of rhabdomyolysis and skin necrosis is a consequence of terlipressine induced severe vasoconstriction. A literature search was performed, in an attempt to identify similar cases as well as other plausible explanations.

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Propofol Dosing Regimens for ICU Sedation Based upon an Integrated Pharmacokinetic– Pharmacodynamic Model

Abstract: Emergence time from sedation with propofol in ICU patients varies with the depth of sedation, the duration of sedation, and the patient's body habitus. Maintaining a light level of sedation ensures a rapid emergence from sedation with long-term propofol administration.

Cited by 144 publications

References 21 publications

Comparison of Dexmedetomidine, Propofol and Midazolam for Short-Term Sedation in Postoperatively Mechanically Ventilated Neurosurgical Patients

Comparison of Dexmedetomidine, Propofol and Midazolam for Short-Term Sedation in Postoperatively Mechanically Ventilated Neurosurgical Patients

Modeling of the Sedative and Airway Obstruction Effects of Propofol in Patients with Parkinson Disease undergoing Stereotactic Surgery

Terlipressine Induced Rhabdomyolysis After Orthotopic Liver Transplantation

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