Pharmacokinetics of eltanolone in male and female patients following intravenous bolus injection

BACKGROUND: The pharmacokinetics of the steroid anesthetic eltanolone have been studied in male volunteers. However, steroids may exhibit gender-related differences in pharmacokinetics and surgery may alter drug disposition. METHODS: Male (n = 12) and female (n = 9) ASA 1-2 patients (age 26-45 yrs) undergoing discectomy with microsurgical technique were included. Anesthesia was induced with eltanolone 0.75 mg/kg and maintained with nitrous oxide, fentanyl and atracurium. Venous blood was sampled for up to 12 h and analyzed for eltanolone and its major metabolites. RESULTS: Induction was smooth and anesthesia uneventful, except that five cases developed a mild transient erythema. Loss of verbal contact occurred within 20-60 s. Pharmacokinetics in one person deviated significantly from the rest of the subjects. No difference between groups with respect to the primary outcome variable noncompartmental clearance (Cl, 1/min) 1.7 vs 1.6, was found. However, the volume of distribution at steady state (Vss, 1/kg) was larger in women (3.1) compared to men (1.3). The pharmacokinetics followed a three-compartment model. The half-lives (min) of the alpha, beta and gamma phases (men vs women, medians) were 1.5 vs 2.2, 42 vs 40 and 222 vs 360, respectively. Area under the curve (AUC, min microgram/l) was 39,810 vs 34,905. Context-sensitive modelling indicated that it may take 10 min more for women than men to recover from an eltanolone infusion of 2 h duration. CONCLUSION: The gender-related differences in the pharmacokinetics of eltanolone were small, and of little clinical significance for induction of anesthesia with eltanolone.     

Further urinary metabolites of delta 1-tetrahydrocannabinol in man

The in vivo metabolism of delta 1-tetrahydrocannabinol (delta 1-THC) was further investigated in man after oral administration. Five dicarboxylic acids were isolated from the urine and identified by gas chromatography-mass spectrometry. None of these acids have been identified in man before and two of them (3",4",5"-trisnor-delta 1-THC-7,2"-dioic acid (15) and 5"-nor-delta 1-THC-7,4"-dioic acid (17)) have hitherto not been found in any species. The major dicarboxylic acid was 4",5"-bisnor-delta 1-THC-7,3"-dioic acid (16) corresponding to 8% of the excreted radioactivity in the urine. The other dicarboxylic acids (14, 18) were present in small amounts.     

Clinical Significance of Specific Gravity of Spinal Anaesthetic Agents Two Double-Blind Studies with Hyperbaric 5% Lidocaine

In two double-blind studies two hyperbaric 5% lidocaine solutions containing glucose in concentrations of 75 mg/ml and 50 mg/ml, respectively, were compared. The onset and total onset time, spread, intensity, duration of analgesia and motor block were studied. The spinal anaesthesia was given with the patient either sitting or in the lateral recumbent position. A tendency to a longer duration of anaesthesia near dermatomes Th X-L II and L IV-L V was noted in the group of patients in the sitting position and receiving lidocaine with a lower glucose concentration. Otherwise there were no differences between the two lidocaine solutions. The result shows that the glucose concentration can be reduced from 75 to 50 mg/ml in "heavy" lidocaine without any clinical disadvantage. This means a more isotonic solution in relation to the cerebrospinal fluid, resulting in milder osmotic effects on interspinal structures.     

Amino acid infusion induces thermogenesis and reduces blood loss during hip arthroplasty under spinal anesthesia

The thermic effect of amino acids is augmented under general anesthesia and counteracts hypothermia. Mild hypothermia may increase surgical bleeding. We studied whether amino acids also induce thermogenesis under spinal anesthesia and whether this endogenous heat production reduces bleeding during hip arthroplasty. Rectal temperature, oxygen uptake, and perioperative bleeding were measured in 22 patients receiving an IV amino acid mixture (Vamin 18), 240 kJ/h) for 1 h before and then during spinal anesthesia and in 24 control patients receiving acetated Ringer's solution. Blood loss was calculated after surgery by weighing the swabs and the content of the suction tubes after subtraction of the saline used. After surgery, the closed drains were weighed after 24 h. In the amino acid group, the preanesthesia temperature increased by 0.4 degrees C +/- 0.2 degrees C (P < 0.01) and was unchanged in controls. At end of surgery, core temperature had decreased by 0.9 degrees C +/- 0.4 degrees C in controls and by 0.4 degrees C +/- 0.3 degrees C in the amino acid patients (P < 0.01). Oxygen uptake increased by 26 +/- 7 mL/min, or 16% +/- 5% (P < 0.05), from baseline in the amino acid patients, whereas it was unchanged in the controls. Blood loss during surgery was significantly larger in the control patients (702 +/- 344 mL) than in the amino acid patients (516 +/- 272 mL) (P < 0.05). After surgery, there were no significant differences in shed blood volume. In conclusion, amino acid infusion also induced a thermogenic response under spinal anesthesia. In addition, the prevention of temperature decrease during spinal anesthesia seemed to have a positive effect on intraoperative blood loss. IMPLICATIONS: Infusion of a balanced mixture of amino acids during spinal anesthesia prevented core body temperature decrease. Bleeding was also less pronounced.     

Carbonic anhydrase inhibitor sulthiame reduces intracellular pH and epileptiform activity of hippocampal CA3 neurons

PURPOSE: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame's anticonvulsant properties. METHODS: The effects of sulthiame (a) on pHi of 2',7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxymetyl ester (BCECF-AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 microM 4-aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide. RESULTS: In the majority of neurons, sulthiame (1.0-1.5 mM; n = 8) as well as the membrane permeant acetazolamide (0.5-1.0 mM; n = 6) reversibly decreased pHi by 0.18 +/- 0.05 (SD) and 0.17 +/- 0.10 (SD) pH units, respectively, within 10 min. The poor membrane permeant benzolamide (1.0-2.0 mM) had no influence on pHi (n = 8). Sulthiame (1.0-2.5 mM) and acetazolamide (1.0-2.0 mM) reversibly reduced the frequency of action potentials and epileptiform bursts after 10-15 min (n = 9, n = 7), whereas benzolamide (1.0-2.0 mM) had no effect (n = 6). CONCLUSIONS: The results suggest that sulthiame acts as a membrane-permeant CA inhibitor whose beneficial effect on epileptiform activity results at least in part from a modest intracellular acidosis of central neurons.     

Longitudinal stress fracture: patterns of edema and the importance of the nutrient foramen

DESIGN AND PATIENTS: We reviewed the MR appearances of six cases of longitudinal stress fracture of the lower extremity. RESULTS: One fracture was in the femur and five were in the tibia. Four of the tibial fractures showed edema starting in the mid-tibia at the level of the nutrient foramen with the fracture on the anteromedial cortex. The other tibial fracture started at the nutrient foramen. Three fractures (two tibial and the femur fracture) showed eccentric marrow edema; all fractures showed either eccentric periosteal reaction or soft tissue edema. CONCLUSION: Primary diagnosis of longitudinal stress fracture is made by finding a vertical cleft on one or more axial images. Secondary signs of position of the nutrient foramen and patterns of edema may be useful.     

Lateral position reduces blood loss in hip replacement surgery: a prospective randomized study of 74 patients

We performed a prospective randomized study of 74 patients undergoing hip replacement surgery and compared the perioperative blood loss in the lateral position with that in the supine position. The surgeons and surgical technique were the same in the two groups. The patients operated on in the lateral position had a significantly lower total blood loss, on average 201 ml less.