| Influencia de la obesidad sobre la farmacocinética del propofol: derivación de un modelo farmacocinético |
Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model.
Cortínez LI, Anderson BJ, Penna A, Olivares L, Muñoz HR, Holford NH, Struys MM, Sepulveda P.
Departamento de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Hospital Clínico U. Católica, Marcoleta 367, PO Box 114-D, Santiago, Chile. licorti@med.puc.cl
Br J Anaesth. 2010 Oct;105(4):448-56. Epub 2010 Aug 14.
Abstract
BACKGROUND: The objective of this study was to develop a pharmacokinetic (PK) model to characterize the influence of obesity on propofol PK parameters. METHODS: Nineteen obese ASA II patients undergoing bariatric surgery were studied. Patients received propofol 2 mg kg(-1) bolus dose followed by a 5-20-40-120 min, 10-8-6-5 mg kg(-1) h(-1) infusion. Arterial blood samples were withdrawn at 1, 3, 5 min after induction, every 10-20 min during propofol infusion, and every 10-30 min for 2 h after stopping the propofol infusion. Arterial samples were processed by high-performance liquid chromatography. Time-concentration data profiles from this study were pooled with data from two other propofol PK studies available at http://www.opentci.org. Population PK modelling was performed using non-linear mixed effects model. RESULTS: The study involved 19 obese adults who contributed 163 observations. The pooled analysis involved 51 patients (weight 93 sd 24 kg, range 44-160 kg; age 46 sd 16 yr, range 25-81 yr; BMI 33 sd 9 kg m(-2), range 16-52 kg m(-2)). A three-compartment model was used to investigate propofol PK. An allometric size model using total body weight (TBW) was superior to all other models investigated (linear TBW, free fat mass, lean body weight, normal fat mass) for all clearance parameters. Variability in V2 and Q2 was reduced by a function showing a decrease in both parameters with age. CONCLUSIONS: We have derived a population PK model using obese and non-obese data to characterize propofol PK over a wide range of body weights. An allometric model using TBW as the size descriptor of volumes and clearances was superior to other size descriptors to characterize propofol PK in obese patients.
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| Efectos de las concentraciones en sitio de remifentanil en el mantenimiento de la homeostasis cardiovascular en respuesta al estímulo quirúrgico durante la anestesia con propofol guiada con BIS en pacientes seriamente obesos. |
Effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index guided propofol anesthesia in seriously obese patients.
Albertin A, La Colla G, La Colla L, Bergonzi PC, Deni F, Moizo E.
Department of Anesthesiology, IRCCS H. San Raffaele, Vita-Salute University of Milan, Milan, Italy. albertin.andrea@hsr.it
Minerva Anestesiol. 2006 Nov;72(11):915-24.
Abstract
AIM: The aim of this prospective study was to determine the effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index (BIS) guided propofol anesthesia in seriously obese patients. METHODS: Twenty-two patients, female/male 15/7, ASA physical status II - III, aged 29-69 years, body mass index (BMI) 54.5+/-12, undergoing major open bariatric surgery, were enrolled to receive a propofol-remifentanil total intravenous anesthesia. All patients were intubated by using a flexible fiberoptic bronchoscopic technique facilitated by a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. After endotracheal intubation, anesthesia was started with a target controlled infusion of propofol initially set at 6 microg/mL, then adjusted to maintain a BIS value between 40 and 50. The mean effect site concentration of remifentanil was recorded at different intervals time during surgery: skin incision-opening of peritoneum (T1), bowel resection (T2), cholecystojejunal anastomosis (T3), ileojejunal anastomosis (T4), closing of peritoneum (T5). RESULTS: The mean plasma concentrations of propofol required to maintain a BIS value between 40 and 50 were 4+/-0.55, 3.8+/-0.64, 3.8+/- 0.63, 3.8+/-0.65 and 3.8+/-0.63 microg/mL at T1, T2, T3, T4 and T5 interval time, respectively. The mean values of remifentanil target effect site concentration were 5.2+/-1.3, 7.7+/-1.7, 9.1+/-1.8, 9.7+/- 2.2 and 9.9+/-2.5 ng/mL at T1, T2, T3, T4 and T5 interval time. CONCLUSIONS: This study suggests that tolerance to remifentanil infusion is profound and develops very rapidly in morbidly obese patients submitted to open bariatric surgery during BIS guided propofol anesthesia. The administration of opiates during anesthesia based on target-controlled infusion should include corrections for the development of tolerancehttp://www.minervamedica.it/en/getfreepdf/ZOSA%252BA9LOLjgCQTSBOMAEvIT2ZMiR5o1I%252BEFcCh1Ko9GGU8ay27fLzd6uHpEWpvrqXn6sT9JXwQqRnyLnMOKag%253D%253D/R02Y2006N11A0915.pdf
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| Rendimiento predictivo del la ¨formula de Servin¨ durante la infusión de propofol-remifentanil controlada al órgano blanco y guiada con BIS en obesos mórbidos |
Predictive performance of 'Servin's formula' during BIS-guided propofol-remifentanil target-controlled infusion in morbidly obese patients.
Albertin A, Poli D, La Colla L, Gonfalini M, Turi S, Pasculli N, La Colla G, Bergonzi PC, Dedola E, Fermo I.
Department of Anaesthesiology--IRCCS San Raffaele, Milan, Italy. albertin.andrea@hsr.it
Br J Anaesth. 2007 Jan;98(1):66-75. Epub 2006 Nov 27.
Abstract
BACKGROUND: The aim of this study was to assess the predictive performance of 'Servin's formula' for bispectral index (BIS)-guided propofol-remifentanil target-controlled infusion (TCI) in morbidly obese patients. METHODS: Twenty patients (ASA physical status II-III, age 32-64 yr) undergoing bilio-intestinal bypass surgery, were recruited. Anaesthesia was induced by using a TCI of propofol with an initial target plasma concentration of 6 microg ml(-1), then adapted to maintain stable BIS values ranging between 40 and 50. A TCI of remifentanil was added to achieve pain control and haemodynamic stability. For propofol, weight was corrected as suggested by Servin and colleagues. With ideal body weight (IBW) corrected according to formula suggested by Lemmens and colleagues. For remifentanil, weight was corrected according to IBW. Arterial blood samples for the determination of blood propofol concentrations were collected at different surgical times. The predictive performance of propofol TCI was evaluated by examining performance accuracy. RESULTS: Median prediction error and median absolute prediction error were -32.6% (range -53.4%; -2.5%) and 33.1% (10.8%; 53.4%), respectively. Wobble median value was 5.9% (2.5%; 25.2%) while divergence median value was -1.5% h(-1) (-7.7; 33.8% h(-1)). CONCLUSION: Significant bias between predicted and measured plasma propofol concentrations was found while the low wobble values suggest that propofol TCI system is able to maintain stable drug concentrations over time. As already suggested before, a computer simulation confirmed that the TCI system performance could be significantly improved when total body weight is usedhttp://bja.oxfordjournals.org/content/98/1/66.full.pdf+html
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