Premises of creation of Internet portal designed to provide access to participants of educational and scientific process for the joint creation, consolidation, concentration and rapid spreading of educational and scientific information resources in its own depository are considered. CMS-based portal content management systems’ potentiality is investigated. Architecture for Internet portal of MES of Ukraine’s information resources is offered.

Створення порталу інформаційно-довідкових ресурсів міністерства освіти і науки україни

The acute central nervous and cardiovascular effects of the local anesthetics ropivacaine and bupivacaine were compared in 12 volunteers in a randomized double-blind manner with use of intravenous infusions at a rate of 10 mg/min up to a maximal dose of 150 mg. The volunteers were all healthy men. They were familiarized with the central nervous system (CNS) toxic effects of local anesthetics by receiving a preliminary intravenous injection of lidocaine. The infusions of ropivacaine and bupivacaine were given not less than 7 days apart. CNS toxicity was identified by the CNS symptoms and the volunteers were told to request that the infusion be stopped when they felt definite but not severe symptoms of toxicity such as numbness of the mouth, lightheadedness, and tinnitus. In the absence of definite symptoms, the infusion was stopped after 150 mg had been given. Cardiovascular system (CVS) changes in conductivity and myocardial contractility were monitored using an interpretive electrocardiograph (which measured PR interval, QRS duration, and QT interval corrected for heart rate) and echocardiography (which measured left ventricular dimensions from which stroke volume and ejection fraction were calculated). Ropivacaine caused less CNS symptoms and was at least 25% less toxic than bupivacaine in regard to the dose tolerated. Both drugs increased heart rate and arterial pressure. Stroke volume and ejection fraction were reduced. There was no change in cardiac output. Although both drugs caused evidence of depression of conductivity and contractility, these appeared at lower dosage and lower plasma concentrations with bupivacaine than with ropivacaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Toxicity of Ropivacaine Compared with That of Bupivacaine

BackgroundThe authors sought to confirm a chance observation that intravenous lipid treatment increases the dose of bupivacaine required to produce asystole in rats. The authors also measured the partitioning of bupivacaine between the lipid and aqueous phases of a plasma-lipid emulsion mixture.Meth

Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats.

BackgroundAnesthesia-related complications are the sixth leading cause of pregnancy-related death in the United States. This study reports characteristics of anesthesia-related deaths during obstetric delivery in the United States from 1979–1990.MethodsEach state reports deaths that occur within 1 y

Anesthesia-related deaths during obstetric delivery in the United States, 1979-1990.

Maximum recommended doses of local anesthetics: a multifactorial concept.

The acute intravenous cardiovascular toxicity of five amide local anesthetic agents was studied in intact, ventilated dogs anesthetized with pentobarbital. Minimal changes in various cardiovascular functions were seen at doses of 0.3 to 3.0 mg/kg. At 10 mg/kg profound hypotension accompanied by sign

Acute Cardiovascular Toxicity of Intravenous Amide Local Anesthetics in Anesthetized Ventilated Dogs

Ropivacaine (S-(-)-1-propyl-2',6'-pipecoloxylidide) is a new local anesthetic that is structurally related to mepivacaine and bupivacaine. The comparative effects of ropivacaine and bupivacaine on motor function were assessed in the laboratory rat and dog. (It was not possible to accurately evaluate sensory blockade in these models.) Several concentrations of both agents were injected in the region of the sciatic nerve of the rat and into the lumbar epidural or subarachoid space in the dog. Epidural blockade was also performed utilizing solutions of ropivacaine and bupivacaine which contained epinephrine (1:200,000). The rat sciatic block studies indicate that at concentrations of 0.5 and 0.75%, ropivacaine had a slightly shorter time of onset and duration of motor blockade than did bupivacaine. In the epidural and spinal studies in the dog, ropivacaine was less potent and had a shorter duration of motor blockade than did bupivacaine at equal drug concentrations. A 1.0% solution of ropivacaine produced epidural motor blockade similar in onset and duration to that achieved with a 0.75% solution of bupivacaine. Epinephrine did not significantly prolong the duration of motor blockade of either agent after epidural administration.

Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog.

The comparative central nervous system (CNS) toxicity of serially administered intravenous doses of lidocaine, bupivacaine, etidocaine, and tetracaine was investigated in awake dogs. The mean cumulative dose required for convulsive activity was 4.0 mg/kg tetracaine, 5.0 mg/kg bupivacaine, 8.0 mg/kg etidocaine, and 22.0 mg/kg lidocaine. The cumulative convulsive dose of lidocaine was significantly greater than that of the other three agents (P less than 0.01). A comparison of the in vivo anesthetic potency and the acute CNS toxicity of these various agents suggests little difference in the therapeutic ratio between less potent anesthetics such as lidocaine and more potent drugs, i.e., tetracaine, bupivacaine, and etidocaine. The relative CNS toxicity of the different agents as determined in awake dogs in this study was compared with their relative cardiovascular toxicity previously evaluated in a series of ventilated dogs anesthetized with pentobarbital. The dose of lidocaine, etidocaine, tetracaine, and bupivacaine required to produce irreversible cardiovascular depression was 3.5-6.7 times greater than that which produced convulsions. These results suggest that the CNS is the primary target organ for the toxic effects of both highly lipid-soluble and highly protein-bound local anesthetics (i.e., bupivacaine, etidocaine, and tetracaine) and less lipid-soluble and less protein-bound drugs (i.e., lidocaine) following rapid intravenous administration.

Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid intravenous administration.

Two groups of six beagle dogs received rapid intravenous (IV) injections of ropivacaine or bupivacaine on two occasions in a blinded random fashion. Initially, a dose sufficient to cause convulsions (CD) was given followed by twice the CD (2 x CD), which was administered 48 h later. The CD of bupivacaine (4.3 mg/kg) and ropivacaine (4.9 mg/kg) caused significant (P less than 0.05) increases in heart rate and mean arterial blood pressure. There was no difference between drug groups. Seizures were abolished by 10 mg/kg of intravenous thiamylal. Endotracheal intubation and controlled respiration with O2-enriched air with no other treatment resulted in rapid and complete recovery in all dogs. All dogs receiving 2 x CD of bupivacaine (8.6 mg/kg) or ropivacaine (9.8 mg/kg) were initially treated with thiamylal and mechanical ventilation. Two dogs in the bupivacaine group developed hypotension, respiratory arrest, ventricular tachycardia, and ventricular fibrillation, which were resistant to closed chest cardiac massage, treatment with epinephrine, bretylium, and atropine, and direct current cardioversion. The four remaining dogs in the infusion group were successfully resuscitated. All of the animals in the ropivacaine-treated group survived the administration of the 2 x CD dose. Mild hypotension developed in one dog and was treated with intravenous epinephrine (0.75 mg). This resulted in nodal tachycardia, which was abolished after treatment with bretylium. Another dog had two 1-s bursts of premature ventricular contractions requiring no treatment. The rapid treatment of convulsions and cardiovascular toxicity resulted in a decreased number of deaths in both groups when compared with dogs from a previously published study in which no therapy was instituted. Thus, early aggressive treatment of central nervous system and cardiovascular system toxicity is capable of reducing the incidence of mortality associated with the rapid intravenous administration of excessive doses of local anesthetics.

Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog.

The relative central nervous system and cardiovascular toxicity of bupivacaine was compared in pregnant and nonpregnant ewes during continuous infusion of bupivacaine into the jugular vein at the rate of 0.5 mg. kg-1. min-1. In all animals, identical symptoms of toxicity occurred in the following order: convulsions, hypotension, respiratory arrest, and circulatory collapse. The dose of bupivacaine required to produce central nervous system (CNS) toxicity in the pregnant ewe tended to be lower than in the nonpregnant animal, although the difference was not statistically significant (P < 0.1). However, the mean dose of bupivacaine resulting in cardiovascular collapse was significantly lower in pregnant ewes (5.1 ± 0.7 mg/kg) than in nonpregnant animals (8.9 ± 0.9 mg/kg). Similarly, bupivacaine blood concentrations at the onset of respiratory arrest and circulatory collapse were lower in the pregnant group, being 5.2 ± 0.7 μg/ml and 5.5 ± 0.8 μg/ml, respectively, versus 7.5 ± 1.0 μg/ml and 8.0 ± 0.9 μg/ml, respectively, in the nonpregnant group (P < 0.05). The concentration of bupivacaine in the brain of pregnant ewes at the time of cardiovascular collapse was significantly lower (P < 0.01) than in the nonpregnant group (7.5 ± 1.5 vs. 16.3 ± 1.7 μg/g). The myocardial tissue concentration of bupivacaine also tended to be lower in the pregnant group, although the differences were not statistically significant (P < 0.1). Comparisons of bupivacaine doses and blood concentrations associated with the onset of convulsions and circulatory collapse (CC/CNS ratio) with those of lidocaine, reported previously, indicate that a narrower margin of safety exists following administration of bupivacaine in nonpregnant sheep. These ratios were 3.7 ± 0.5 and 1.6 ± 0.1, respectively, for bupivacaine and 7.1 ± 1.1 and 3.6 ± 0.3, respectively, for lidocaine. In addition, the data indicate that the pregnant sheep may be more sensitive to the cardiotoxic effects of bupivacaine than the nonpregnant animal.

H. S. Feldman

Papers

Acute Cardiovascular Toxicity of Intravenous Amide Local Anesthetics in Anesthetized Ventilated Dogs

Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog.

Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid intravenous administration.

Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog.

Bupivacaine toxicity in pregnant and nonpregnant ewes.