Cardiopulmonary parameters in propofol- or thiopental-anesthetized dogs induced to pulmonary hypertension by serotonin / Parâmetros cardiopulmonares em cães anestesiados com propofol ou tiopental e induzidos à hipertensão pulmonar pela serotonina

The cardiopulmonary changes in propofol- or thiopental-anesthetized dogs induced to pulmonary hypertension (PH) were evaluated. Twenty adult animals were randomly assigned to two groups: propofol group (PG) and thiopental group (TG). In PG, propofol was used for induction (8(0.03mg.kg-1) and anesthesia maintenance (0.8mg.kg-1.minute-1), while, in TG, thiopental was used (22±2.92mg.kg-1; 0.5mg.kg-1.minute-1, respectively). Mechanical ventilation using time cycle was started. PH was induced by administration of serotonin (5HT) (10µg.kg-1 and 1mg.kg-1.hour-1) through a thermodilution catheter positioned in the pulmonary artery. The measurements were performed before administration of 5HT (T0), after 30 minutes (T30), then at 15-minute intervals (T45, T60, T75 and T90). No differences between groups were registered for systolic (sPAP) and mean pulmonary arterial pressure (mPAP), mean arterial pressure (MAP), total peripheral resistance index (TPRI) and pulmonary vascular resistance index (PVRI). In PG, sPAP and mPAP increased from T30. While in TG, sPAP and mPAP increased from T75. In PG, heart rate (HR) increased from T30, in which PG was higher than TG. The TPRI values decreased from T30 in PG, and in TG, at T45, T60 and T90. In PG, at T0, PVRI was lower than at other times. In PG, arterial partial pressures of oxygen (PaO2) decreased from T60 and alveolar-arterial oxygen gradient (PA-aO2) increased at T60. In TG, at T0 PaO2 was higher than at T30, T45, T60 and T90, while PA-aO2 at T0 was lower than at T90. From T30 to T90, TG showed higher PaO2 means and lower arterial partial pressures of carbon dioxide (PaCO2) values when compared to PG. In PG, from T30, PaCO2 increased, while in TG this parameter was stable. In conclusion, thiopental anesthesia attenuated the cardiopulmonary changes resulting from serotonin-induced PH, probably by attenuation of vasoconstriction and bronchoconstriction.

Avaliaram-se as alterações cardiopulmonares em cães anestesiados com propofol ou tiopental induzidos à hipertensão pulmonar (HP). Vinte animais adultos foram distribuídos aleatoriamente em dois grupos: grupo propofol (PG) e grupo tiopental (TG). No PG, o propofol foi usado para indução (8(0,03mg.kg-1) e manutenção da anestesia (0,8mg.kg-1minuto-1), enquanto no TG foi empregado o tiopental (22(2,92mg.kg-1; 0,5mg.kg-1.minute-1, respectivamente). Em seguida, a ventilação mecânica ciclada a tempo foi iniciada. A HP foi induzida pela administração de serotonina (5HT) (10µg.kg-1e 1mg.kg-1.hour-1) por meio de cateter de termodiluição posicionado na artéria pulmonar. As mensurações tiveram início antes da administração da 5HT (T0), depois de 30 minutos (T30), seguida de intervalos de 15 minutos (T45, T60, T75 e T90). Diferenças entre os grupos não foram registradas para pressões sistólica (PAPs) e média (PAPm) da artéria pulmonar, pressão arterial média (PAM), índices da resistência periférica total (IRPT) e da resistência vascular pulmonar (IRVP). A PAPs e a PAPm aumentaram a partir de T30, no PG, e a partir de T75, no TG. No PG, a frequência cardíaca (FC) aumentou a partir de T30, no qual PG foi maior que TG. O IRPT diminuiu no T45, T60 e T90, no TG, e a partir de T30 no PG. No PG, no T0, IRVP foi menor que nos outros momentos. No PG, a pressão parcial de oxigênio no sangue arterial (PaO2) diminuiu a partir de T60, e a diferença de tensão entre o oxigênio alveolar e arterial (PA-aO2) aumentou no T60. No TG, no T0, a PaO2 foi maior que no T30, T45, T60 e T90, enquanto a PA-aO2,, no T0, foi menor que no T90. Entre T30 e T90, TG apresentou maior PaO2 e menor pressão parcial de dióxido de carbono no sangue arterial (PaCO2) quando comparado ao PG. No PG, a partir de T30, a PaCO2 aumentou. A anestesia com tiopental abrandou as mudanças cardiopulmonares resultantes da indução da HP pela serotonina, provavelmente devido à atenuação da vasoconstrição e broncoconstrição.

Suicide by self-administration of a drug mixture (propofol, midazolam, and zolpidem) in an anesthesiologist: the first case report in Italy.

The authors report an unusual case of suicide of an anesthesiologist, in which the suicide manner and means depend upon the victim's occupation. This is the first case report published in Italy of a death involving propofol and other drugs. The anesthesiologist was found dead with an empty drip still inserted in the hand and another one near his body. Forensic and toxicological findings suggested that the cause of death was a respiratory depression due to a self-administration of a rapidly infused lethal drug mixture. Analytical drug quantification was performed by gas chromatography-mass spectrometry. Blood analysis revealed: zolpidem (0.86 µg/mL), propofol (0.30 µg/mL), midazolam (0.08 µg/mL), thiopental (0.03 µg/mL), and amitriptyline (0.07 µg/mL). Adipose tissue and hair analysis suggested a previous and repeated use of these drugs verifying the fact that in Italy recreational abuse of anesthetic and sedative agents in health care practitioners is becoming an increasing problem.

Membrane sensors for the selective determination of thiopental.

Novel miniaturized polyurethane (PU) membrane sensors in an all-solid state graphite support were developed, electrochemically evaluated and used for the assay of thiopental drug. The thiopental (T) sensors are based on the formation of ion-association complexes of thiopental with copper(II) and cobalt(II)-bathophenanthroline (bphen) counter anions as electroactive materials dispersed in a polyurethane matrix. The sensors show a linear response for thiopental over the range of 1 x 10(-1) - 5 x 10(-5) M thiopental at 25 degrees C over the pH range 6 - 11 with anionic slopes of -28.7 and -28.3 mV decade(-1) with Cu- and Co-bphen thiopental membrane sensors, respectively. These sensors exhibit a fast response time (25 - 45 s), a low detection limit (5 x 10(-6) M), a long lifetime (7 weeks) and good stability. The selectivity coefficients for thiopental sensors relative to the number of interfering anions, were investigated. These sensors were used for the direct potentiometry of thiopental in a pharmaceutical formulation and human serum. Results with mean accuracy of 99.8 +/- 0.5% of nominal were obtained, which compare well with data obtained using spectrophotometric (UV-Vis) and British Pharmacopoeia (BP) methods.

Detection of thiopental and pentobarbital in head and pubic hair in a case of drug-facilitated sexual assault.

The quali-quantitative determination of two barbiturates, thiopental and its metabolite pentobarbital, in head and pubic hair samples of a woman who had been sexually assaulted during hospitalisation, is reported. Hair was analysed by means of solid-phase microextraction (SPME) and gas chromatography-multiple mass spectrometry (GC-MS-MS), in chemical ionisation conditions. Thiopental and pentobarbital were found in three proximal head hair segments (sample 1A: 0.30 and 0.40 ng/mg; sample 1B: 0.20 and 0.20 ng/mg; sample 3: 0.15 and 0.20 ng/mg) and pubic hair sample. Two distal head hair segments were negative for both barbiturates. Despite the lack of collection and toxicological analysis of blood or urine samples within the hospital setting, analytical findings from hair revealed the use of the anaesthetic agent thiopental to sedate the victim quickly and deeply and commit sexual assault.

Evidence of polydrug use using hair analysis: a fatal case involving heroin, cocaine, cannabis, chloroform, thiopental and ketamine.

A case is presented involving a young woman on several illicit drugs (heroin, cocaine and cannabis) as well as two medications and a solvent used for their anesthetic and narcotic properties: thiopental, ketamine and chloroform. This complex drug use was supported by hair analysis over a 10.5 cm segment of the hair taken at autopsy. The average measured concentrations in hair were: thiopental = 5.3 ng/mg, pentobarbital = 10.0 ng/mg, ketamine = 11.3 ng/mg norketamine = 1.0 ng/mg, diazepam = 1.2 ng/mg, nordiazepam = 0.1 ng/mg, 6-acetylmorphine = 4.4 ng/mg, morphine = 3.4 ng/mg, codeine = 1.2 ng/mg, cocaine = 5.5 ng/mg, benzoylecgonine = 1.5 ng/mg and methylecgonine ester = 1.0 ng/mg. While the ketamine/norketamine ratio is consistent with that already reported on drug detection in hair, the thiopental/pentobarbital ratio seems to be inverted.

Estudio comparativo entre propofol y tiopental para intervenciones quirúrigicas de corta duración

En 20 pacientes ASA 1 Y 2 se comparan las condiciones de recuperación utilizando propofol (2.0 mg/kg) o tiopental (3 mg/kg) , como agentes anestésicos principales para cirugías de corta duración. El tiempo de ápnea fue más prolongado para el grupo propofol con una media de 132 segundos, mientras que con el tiopental fue de 50.6 segundos. En el grupo propofol se comprobó un descenso de la presión arterial diatólica de un 10 por ciento a los dos minutos de la inducción anestésica, retornando a los valores normales a los 10 minutos. El tiempo de recuperación para sentarse fue significativamente menor para el grupo propofol (13,8 minutos) que para el grupo tiopental (13.8 minutos ). Esta diferencia se acentúa cuando se considera el intervalo entre la finalización de la operación y la cpacidad de pararse sin ayuda (21.9 minutos) vs 59.1 minutos) La calidad de la anestesia fue superior para el grupo propofol en una significancia estadística de 99 por ciento. La anestesia postoperatoria fue excelente en los dos grupos. En el grupo propofol una paciente presentó náusea, a diferencia del grupo tiopental; en que tres pacientes presentaron vómito y/o náusea, cefálea una paciente, mareo cuatro pacients y somnolencia 8 pacientes...

High-performance liquid chromatographic method for determining thiopental concentrations in twelve rat tissues: application to physiologic modeling of disposition of barbiturate.

A sensitive, selective and reproducible high-performance liquid chromatographic assay of thiopental concentrations in twelve rat tissues was developed using thiamylal as the internal standard. Samples were homogenized in phosphate buffer, extracted into pentane and chromatographed on a microparticulate octadecyl reversed-phase column using ultraviolet detection at 290 nm. A simple digestive step with collagenase prior to homogenization facilitated analysis of thiobarbiturate in skin. Thiopental extraction recovery from fat exceeded 90%. Assay sensitivity was greater than 1 microgram/ml for tissue and plasma samples as small as 50 microliters. This assay has been applied to physiologic pharmacokinetic studies. The paper also presents typical concentration-time profiles of thiopental in four tissues taken from 74 rats given 20 mg/kg thiopental.

Toxicological study on intravenous thiopental anesthesia--interrelation between rate of injection and distribution of thiopental.

A simple, rapid and accurate method to extract and clean thiopental in biological materials rich in fat was developed by using a separation column packed with Extrelut and Florisil. A Quantitative determination of thiopental by means of a gas chromatograph equipped with a flame photometric sulfur detector was attempted. The calibration curve was linear over the range of 5-200 micrograms/ml. Extraction of replicate tissues involving 3 micrograms of thiopental resulted in a recovery of the 99.7-101.8% range and a coefficient of deviation of the 0.3-1.9% range. Replicate extraction of five tissues from rats treated with thiopental resulted in a coefficient of deviation of below 6%. In rats given 40 mg/kg of thiopental and sacrificed after 5 min, the thiopental levels in fat were found to be higher after a slow intravenous injection than after a quick injection. The same tendency, however, was not observed in other tissues. It seems that the rate of intravenous thiopental injections might be estimated by comparison with thiopental levels in fat tissues.

Concentrations of thiopentone in mature breast milk and colostrum following an induction dose.

In two groups of eight patients, concentrations of thiopentone in mature breast milk and colostrum following anaesthesia induction with 5.4 and 5.0 mg kg-1 b.w. (mean), respectively, were measured in the first 36 h postoperatively. Blood concentrations were measured simultaneously. The maximal concentrations were: in mature breast milk, 3.4 +/- 0.68 mumol l-1 (mean +/- s.e. mean) (0.090 mg 100 ml-1), and in colostrum, 1.3 +/- 0.5 mumol l-1 (0.034 mg 100 ml-1). The milk/plasma ratio was less than 1.0 in both groups. The above concentrations may be regarded as negligible and therefore non-toxic for the nursing infant.

Postmortem stability of barbiturates in blood and tissues.

The stability of five commonly prescribed barbiturates and thiopental in blood and liver at room temperature and at 4 degrees C was studied. Gas chromatography was used for oxybarbiturate analysis while liquid chromatography was used to quantitate thiopental. In blood and liver, greater than 75% of the drugs were detected at the end of the two- to three-month period. These changes were not considered significant; therefore, barbiturates appear to be stable in blood and liver under the conditions of these experiments.

Liquid chromatographic analysis of thiopental in blood and tissues.

A liquid chromatographic method for the quantitation of thiopental in blood and tissues is presented. Quantitation in blood utilizes a single step dichloromethane extraction at pH 5.5. After mixing and centrifugation, the organic layer is evaporated to dryness at 40 degrees C and the residue reconstituted with methanol. Tissue extraction includes an alkaline clean-up step followed by re-extraction with dichloromethane after acidification. Either of two 10 mu columns can be used: a C8 or a C18 column. The mobile phase was methanol:water (60:40) at a flow of 2 mL/min. The wavelength of detection was 290 nm. Thiopental can be detected to 1 mg/L using this procedure, and no interferences with other acidic or neutral drugs were found.

Dose of thiopental, pentobarbital, and phenytoin for maximal therapeutic effects in cerebral ischemic anoxia.

Recent interest in pharmacotherapy for various cerebral insults with potentially dangerous drugs, such as barbiturate anesthetics, has created a need to determine the lowest or optimal dose resulting in maximal therapeutic effects. Our earlier studies suggested that whole brain free fatty acid (FFA) accumulation during complete global ischemia reflects the evolution of brain damage. Various drugs effective in ameliorating ischemic brain injury were also effective in attenuating FFA accumulation. The degree of attenuation by a given drug at various doses may indicate the optimal dose. We studied the attenuation of whole brain FFAs (i.e., 20:4, 18:0, 18:1, and 16:0) by 15-120 mg/kg of thiopental or pentobarbital, or 50-300 mg/kg of phenytoin or ketamine intraperitoneal (IP), during 10-min decapitation ischemia in rats. Plasma and brain drug levels were measured except ketamine. Maximal attenuation of FFAs occurred at pentobarbital, thiopental, and phenytoin doses of 15, 30, and 150 mg/kg IP reducing total FFA by 18, 22, and 31%, respectively. These results indicate that maximal therapeutic effects are obtained at subanesthetic doses of barbiturates and at the anticonvulsant dose of phenytoin.

A suicide by pancuronium bromide injection: evaluation of the fluorometric determination of pancuronium in postmortem blood, serum and urine.

A fatal case of suicidal injection of pancuronium bromide is presented. Pancuronium was detected in blood and urine by ion-pair extraction and fluorometry. An evaluation of the fluorometric procedure for the determination of pancuronium in postmortem blood, serum and urine is presented. Stability of the extracted ion-pair, possible interferences from other drugs, and the effects of specimen storage were studied.

Determination of thiopental by high pressure liquid chromatography.

A specific and rapid reverse phase HPLC-method for the determination of thiopental in serum and in protein free solutions is described. No extraction is used. The detection limit is about 0.090 microgram/ml for serum and about 0.030 microgram/ml for buffer solutions. The retention time is 3.80 min. No interference is found with drugs commonly used in patients with heart diseases. The method was used to follow the serum concentrations in 7 patients who were given thiopental as an introduction to general anaesthesia.

A suicide by thiopentone injection.

Post-mortem tissues from a thiopentone suicide were analysed by ultraviolet spectrometry and gas chromatography. The thiopentone concentrations found (0.6 mg/100 ml of blood and 2 6 mg/100 g of tissue) are consistent with those reported for 'anaesthetic' deaths where only thiopentone and other anaesthetic agents were present. The gas chromatographic method gave more accurate result with the tissues.