Eri Sato

A dopamine infusion decreases propofol concentration during epidural blockade under general anesthesia.

PurposeIt is common clinical practice to use dopamine to manage the reduction in blood pressure accompanying epidural blockade. As propofol is a high-clearance drug, propofol concentrations can be influenced by cardiac output (CO). The purpose of the present study was to investigate the effects of dopamine infusions on propofol concentrations administered by a target-controlled infusion system during epidural block under general anesthesia.Methods12 patients undergoing abdominal surgery were enrolled in this study. Anesthesia was induced with propofol and vecuronium 0.1 mg·kg-1, and maintained using 67% nitrous oxide, sevoflurane in oxygen and constant infusion of propofol. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 6.0 μg·mL-1 at intubation and 2.0 μg·mL-1 after intubation. Before and after the administration of 10 mL of 1.5% mepivacaine from the epidural catheter and dopamine infusion at 5 μg·kg-1·min-1, CO and effective liver blood flow (LBF) were measured using indocyanine green. Blood propofol concentration was also determined using high-performance liquid chromatography.ResultsAt one hour after epidural block and dopamine infusion, CO was significantly increased from 4.30 ± 1.07 L·min-1 to 5.82 ± 0.98 L·min-1 (P < 0.0001), and effective LBF was increased 0.75 ± 0.17 L·min-1 to 0.96 ± 0.18 L·min-1 (P < 0.0001). Propofol concentration was significantly decreased from 2.13 ± 0.24 μg·mL-1 to 1.59 ± 0.29 μg·mL-1 (P < 0.0001). Conclusions: Propofol concentrations decrease with an increase in CO, suggesting the possibility of inadequate anesthetic depth following catecholamine infusion during propofol anesthesia.RésuméObjectifII est courant d’utiliser la dopamine pour traiter la baisse de tension artérielle qui accompagne le bloc péridural. Comme le propofol est un médicament à clairance élevée, sa concentration peut être influencée par le débit cardiaque (DC). Nous avons vérifié les effets de perfusions de dopamine sur les concentrations de propofol administrées par un système de perfusion à concentration cible pendant le bloc péridural sous anesthésie générale.MéthodeDouze patients devant subir une intervention chirurgicale abdominale ont participé à notre étude. L’anesthésie, induite avec du propofol et 0,1 mg·kg-1de vécuronium, a été maintenue avec du protoxyde d’azote à 67 %, du sévoflurane dans de l’oxygène et une perfusion constante de propofol. Le propofol a été administré à tous les sujets par une perfusion à concentration cible pour atteindre 6,0 μg·mL-1 de propofol au moment de l’intubation et 2,0 μg·mL-1 après l’intubation. Avant et après l’administration de 10 mL de mépivacaïne à 1,5 % par le cathéter péridural et la perfusion de dopamine à 5 μg·kg-1·min-1, le CO et le débit sanguin hépatique (DSH) ont été mesurés avec le vert d’indocyanine. La concentration sanguine de propofol a aussi été déterminée par chromatographie liquide haute performance.RésultatsUne heure après le bloc péridural et la perfusion de dopamine, le CO s’était significativement élevé de 4,30 ± 1,07 L·min-1 à 5,82 ± 0,98 L·min-1 (P < 0,0001) et le DSH efficace était accru de 0,75 ± 0,17 L·min-1 à 0,96 ± 0,18 L·min-1 (P < 0,0001). La concentration de propofol a significativement baissé de 2,13 ± 0,24 μg·mL-1 à 1,59 ± 0,29 μg·mL-1 (P < 0,0001).ConclusionLes concentrations de propofol ont diminué avec l’augmentation de CO, ce qui soulève la possibilité d’un niveau anesthésique inadéquat après la perfusion de catécholamine pendant l’anesthésie au propofol.

Plasma concentration for optimal sedation and total body clearance of propofol in patients after esophagectomy

The present study investigated plasma propofol concentration for optimal sedation and total body clearance in patients who required sedation for mechanical ventilation after esophagectomy. Seven patients after esophagectomy were enrolled in this study. Plasma propofol concentrations were measured with high performance liquid chromatography. Total body clearance was calculated from the steady-state concentration. The infusion rate of propofol for achieving the sedation score of level 3 (drowsy, responds to verbal stimulation) was 1.74 ± 0.82 mg kg−1 h−1 (mean ± SD, n = 7) when the plasma propofol concentration and the total body clearance were 0.85 ± 0.24 µg ml−1 and 1.83 ± 0.54 l min−1 (mean ± SD, n =7), respectively.

Influence of landiolol on the dose requirement of propofol for induction of anesthesia

It was reported that the pharmacokinetics of propofol was influenced by cardiac output (CO). The purpose of this study was to evaluate the effect of landiolol (short‐acting beta‐1‐adrenergic blocker) on the dose requirement of propofol for induction of anesthesia. Forty patients were randomly allocated to the control and landiolol group. Induction of anesthesia commenced 10 min after the infusion of 0.9% saline or landiolol, using a Diprifusor set to achieve propofol plasma concentration of 6.0 μg/mL. Induction of anesthesia was defined as the first lack of response to command. Propofol dose was 2.22 ± 0.21 mg/kg for the control group and 1.79 ± 0.28 mg/kg for the landiolol group (P < 0.0001). The quantity of propofol required for the induction of anesthesia was reduced by the administration of landiolol.

Changes in unbound concentration of propofol during hemorrhage

To the Editor: Tirkkonen and Laine recently reported in the Journal that prodrugs such as codeine are often combined with inhibitors of cytochrome P450 (CYP)–activating enzymes in hospital inpatients. Celecoxib (cyclooxygenase 2 inhibitor) was one of the most frequently combined CYP2D6 inhibitors with codeine. We have measured the concurrent use of celecoxib with codeine or other typical CYP2D6 substrates in general practice. Norwegian pharmacists (44 pharmacists from 35 pharmacies) who had been trained on managing drug interactions systematically checked for concurrent substrate use during a 2-month period in 2004 (tramadol not included). An electronic popup notice appeared when celecoxib was registered. Combined substrate use was disclosed by checking the prescription database and consulting the patient. Information about drug doses, prescription history, and any unwanted symptoms declared by the patient was recorded. Celecoxib was dispensed to 764 patients, and 192 events (25%) of concurrent substrate use were found. Codeine, metoprolol, and amitriptyline were the most frequent substrates and represented more than 90% of the findings (Table I). In 50% of cases the prescribing physicians were informed about the interacting potential. One third of the physicians changed the prescription immediately. A similar fraction wished to consider the interaction at the next patient consultation, whereas the remainder did not consider the issue as relevant. Celecoxib at a dosage of 400 mg daily for 7 days has been shown to increase metoprolol exposure by a factor of 1.4 and 2.0 in heterozygous and homozygous extensive CYP2D6 metabolizers, respectively. The most common celecoxib dose in our material was 200 mg daily (Table I), and a study investigating the inhibitory effect of this dosage would have been useful. Nevertheless, about 25% of the patients received 400 mg or more daily (pooled data), which is likely to produce relevant interactions in extensive metabolizers. Pharmacokinetics of codeine and amitriptyline has not been studied with celecoxib, but the exposure of their active form(s) could change substantially during CYP2D6 inhibition. The clinical use of celecoxib is extensive, and it is important to be aware of the high rate of concurrent CYP2D6 substrates. Although the future role of cyclooxygenase 2 inhibitors seems more uncertain after the withdrawal of rofecoxib, further research on celecoxib interactions is warranted.

The effect of gynecologic laparoscopy on propofol concentrations administered by the target-controlled infusion system

The purpose of this study was to assess the effect of gynecologic laparoscopy on propofol concentrations administered by the target-controlled infusion (TCI) system. Thirteen patients undergoing gynecologic laparoscopy (intraabdominal pressure of 10 mmHg) were enrolled in this study. Anesthesia was induced with vecuronium 0.1 mg·kg−1 and propofol, then maintained by 60% nitrous oxide and sevoflurane in oxygen and a constant infusion of propofol. Propofol was administered to all subjects by means of a target-controlled infusion to achieve propofol plasma concentration at 6.0 µg·ml−1 at intubation and 2.0 µg·ml−1 after intubation. Before and during laparoscopy, plasma propofol concentration was determined using high-performance liquid chromatograhy. Cardiac output (CO) and effective liver blood flow (LBF) were also measured using indocyanine green as an indicator. Before and during pneumoperitoneum, there were no significant differences in propofol concentations between each point. Propofol concentrations were well achieved to predicted concentrations administered by the TCI system during gynecologic laparoscopy under propofol and sevoflurane anesthesia.