Early phase pharmacokinetics but not pharmacodynamics are influenced by propofol infusion rate.

BACKGROUND: Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model. METHODS: Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg . kg(-1). h(-1). Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure. RESULTS: Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate. CONCLUSIONS: This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg . kg(-1). h(-1). The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time.

[Report of an inquiry about epidural anesthesia for abdominal aortic aneurysm surgery in Japan].

BACKGROUND: Recently there are growing number of patients suffering from the abdominal aortic aneurysm (AAA), and we have many occasions to anesthetize these patients under coagulation therapy as well. Moreover, the risk of epidural hematoma increases when the operation of the AAA is performed with epidural technique because the operation is usually done with perioperative heparinization. For these reasons, we investigated the current situations of clinical practice in Japan in terms of the epidural anesthesia for AAA surgeries. METHODS: The questionnaires were sent to all 998 Japanese Society of Anesthesiologists certified training hospitals in October 2005, anonymously asking about current practices concerning AAA cases, anesthetic managements, use of epidural anesthesia and the experience of any complications. Fifty one per cent of the total questionnaires were returned and 94% of them could be analyzed. Seventeen per cent of responders were from university institutes or university related hospitals and 75% of them were from general hospitals of secondary critical care centers. RESULTS: This survey showed that the operations of AAA were done at 308 (64% of the responders) hospitals and the total number of AAA surgeries carried out was estimated to be 6,321 the last year. This figure was very close to the number announced by Japan Society of Cardiothoracic Surgeons. The epidural anesthesia was routinely used for AAA surgeries with general anesthesia in 224 hospitals (64%), but it was not used in 51 hospitals (14%). The standard protocol for the application of epidural anesthesia had been installed in 56% of hospitals and mostly in 187 hospitals (as several answers can be chosen). The epidural catheters were inserted the day before operation. There were 113 hospitals in which less than 2 hours was required from epidural puncture to heparinization, but in 141 hospitals it took more than 12 hours. However, on the contrary, many anesthetists answered that the risk of the epidural hematoma had been the cause of not routinely using the epidural anesthesia in AAA operations. We had 30 hospitals in which epidural hematoma had occurred in the cases not limited to AAA surgery and 17 cases of them resulted in severe complications afterwards. CONCLUSIONS: This investigation clarified the current situations of the clinical practice in Japan of the use of epidural anesthesia for AAA surgeries.

[Effects of propofol on hepatic venous oxygen saturation--a comparison with isoflurane or sevoflurane anesthesia].

BACKGROUND: We performed a comparative study of propofol versus isoflurane and sevoflurane using continuous monitoring of hepatic venous oxygen saturation (ShvO2) during upper abdominal surgery in 26 patients. METHODS: Anesthesia was induced with propofol 2-2.5 mg x kg(-1) and vecuronium 0.1 mg x kg(-1). Thereafter, Swan Ganz catheters were inserted into the pulmonary artery and hepatic vein. Group P (n=26) patients received continuous propofol infusion and epidural mepivacaine injection for maintenance, while Group I (n=17) received isoflurane and Group S (n=9) received sevoflurane. Systemic oxygen extraction ratio (OERsys) and hepato-splanchnic oxygen extraction ratio (OERspl) were calculated. RESULTS: Heart rate, mean arterial pressure and cardiac index were unchanged after propofol infusion, and isoflurane or sevoflurane inhalation. Propofol at 8 and 10 mg x kg(-1) x h(-1) significantly decreased ShvO2 and increased OERspl, although isoflurane and sevoflurane did not change them. Mixed venous saturation and OERsys were within normal ranges during the studies. CONCLUSIONS: The results suggest that propofol increases the metabolism and oxygen consumption in the liver.

[The use of epidural ropivacaine for a gravida with disposition for malignant hyperthermia].

It is reported that ropivacaine, a new amide-linked local anesthetic, can be used safely in patients susceptible to malignant hyperthermia. We report a case of the use of epidural ropivacaine for a gravida with disposition for malignant hyperthermia. A 33-year-old female patient, 11 weeks and 2 days pregnant, was admitted for torsion of the right ovarian cyst. Five years before, she had been prepared for operation for uterine myoma. After premedication with atropine 0.5 mg and hydroxyzine 50 mg i.m. her body temperature increased to 39.0 degrees C, and the operation was postponed. By muscle biopsy she was diagnosed susceptible to malignant hyperthermia. Two months thereafter, the operation for uterine myoma was performed under epidural lidocaine and intravenous propofol anesthesia. Three years ago, she had cesarean section under epidural anesthesia using mepivacaine. This time, the epidural catheter was inserted at L 3-4 interspace, and 10 ml of 1.0% ropivacaine was administrated. After fifteen minutes analgesia was obtained to T 10-L 2. Forty minutes later the operation was performed and the patient was safely anesthetized by ropivacaine. Later at 37 weeks and 3 days pregnancy, cesarean section was performed with epidural ropivacaine.