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PubMed1985

Thiobarbiturate-induced histamine release in human skin mast cells.

Human skin mast cell preparations were incubated with thiopental, thiamylal, methohexital, and pentobarbital in concentrations ranging from 10(-5) M to 10(-3) M. Both thiopental- and thiamylal-induced dose-related histamine release, with thiamylal having a significantly greater effect than thiopental (P less than 0.05). In contrast, incubation of skin mast cell preparations with the same concentrations of pentobarbital and methohexital failed to increase histamine release above spontaneous levels at any concentration. The release of histamine by thiopental and thiamylal was not accompanied by the leakage of lactic dehydrogenase (LDH). Although a demonstration of histamine release in vitro is not proof that clinical symptoms are causally related to histamine release in vivo, methohexital may be preferred as the induction agent in patients showing extreme sensitivity to histamine (asthmatics) or increased histamine releasability (atopics).

Anesthetics↗
PubMed1991

Contractile responses of guinea pig trachea to oxybarbiturates and thiobarbiturates.

To determine what mechanisms are involved in barbiturate-induced tracheal constriction and whether a relationship exists between barbiturate structure and the ability of the barbiturate to induce constriction, we compared the effects of thiamylal, thiopental, methohexital, pentobarbital, and phenobarbital at increasing airway tone in an intact guinea pig tracheal preparation in the presence and absence of cyclooxygenase and thromboxane synthetase inhibition. Whole tracheas were suspended between two cannulas in 50-ml tissue baths and perfused at a constant flow rate with Krebs-Henseleit solution. The contractile responses were assessed by measuring the pressure differential between the tracheal inlet and outlet ports. Barbiturates were added to the bath of each trachea, which was washed between each drug. Each drug was added to produce final bath concentrations of 10(-6), 10(-5), 10(-4), 10(-3), and 3 x 10(-3) M. Tracheas were also pretreated with meclofenamate (10(-6) M) (a cyclooxygenase inhibitor) and UK 37,248 (10(-8) to 10(-5) M) and OKY 046 (10(-9) to 10(-6) M) (thromboxane synthetase inhibitors), and the thiamylal protocol was repeated. All data were normalized to a concentration of carbachol (2 x 10(-6) M) that has been shown to produce maximum constriction in this preparation. Thiamylal and thiopental produced constriction beginning at 10(-4) M and reached a maximum at 10(-3) M (P less than 0.0001). Methohexital, pentobarbital, and phenobarbital did not produce any significant change in airway tone. Pretreatment with meclofenamate (10(-6) M), UK 37,248 (5 x 10(-5) M), and OKY 046 (10(-6) M) prevented thiamylal-induced tracheal constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Electrocardiographic interpretation of thiobarbiturate-induced dysrhthymias in dogs.

The cardiac dysrhythmia occuring most commonly during intravenous administration of thiamylal sodium is ventricular bigeminy (ventricular premature depolarization coupled to the preceding sinus beat). Electrocardiographic tracings obtained during thiamylal-induced dyshythmias must be interpreted accurately if an accurate prognosis is to be give. Ventricular bigeminy seemed to originate in the ventricle, distal to the bundle of His. When ventricular premature depolarization was late in diastole, occuring simultaneiously with the next sinus-conducted impulse, a fusion beat resulted. The resultant ventricular bigeminy appeared as: (1) alternating ventricular premature dipolarizations, (2) an electrical alternans, and (3) alternating preexcitation syndrome. This dysrhythmia was associated with palpable alternating strong and weak frmoral arterial pulse. The likelihood that ventricular dysrhythmias will be caused by thiamylal is closely related to dose, concentration, and rate of administration. In a 23-month period, clinical occurrence of ventricular bigeminy during induction of anesthesia with thiamylal was approximately 4%.

Anesthesia, Intravenous↗
PubMed1997

Haemodynamic and catecholamine changes during rapid sevoflurane induction with tidal volume breathing.

PURPOSE: To compare haemodynamic and plasma catecholamine changes with rapid (three minute) inhalational anaesthesia induction with tidal volume breathing of sevoflurane 7%, conventional (seven minute) slow inhalation induction with increasing sevoflurane concentration up to 5%, and induction with thiamylal i.v. METHODS: Twenty-four patients were randomly divided into three groups of eight. In Group A, anaesthesia was induced with tidal volume breathing of sevoflurane 7% (inspiratory concentration) and nitrous oxide 50% in oxygen (total flow; 6 l.min-1) for three minutes: Group B received conventional slow induction for seven minutes and increasing sevoflurane concentration by 0.5% every two or three breaths up to 5% with nitrous oxide 50% in oxygen: and Group C received 5 mg.kg-1 thiamylal with an inhalation of 100% oxygen. Blood pressure, heart rate, rate pressure product, and plasma concentrations of epinephrine and norepinephrine were measured. RESULTS: There were no changes in blood pressure before or after intubation in Group A (sevoflurane 7%) whereas both were increased in patients in Group C (thiamylal). Changes in heart rate and rate pressure product were not different for the two inhalation groups. Plasma epinephrine concentrations decreased in all the three groups. Norepinephrine concentrations were increased before intubation in both inhalation groups but not in the thiamylal group. CONCLUSION: Rapid induction of anaesthesia with sevoflurane 7% and tidal volume breathing for three minutes induced less haemodynamic changes than the other methods studied and has no inhibitory effect on sympathetic activity.

Adult↗
PubMed2003

[Propofol was useful for intractable convulsion in a patient with tetanus: a case report].

An 82-year-old woman with severe tetanus was admitted to our ICU. Anti-convulsive treatment was started by continuous intravenous administration of midazolam followed by thiamylal. On day 15, thiamylal became insufficient to manage the spastic convulsion without frequent intravenous administration of other sedative and muscle relaxants. On day 16, intravenous infusion of propofol was started at the rate of 1 mg.kg-1.h-1. Propofol was more effective than thiamylal to treat convulsion and to stabilize the sympathetic nerve activity. Propofol was also effective to achieve the better general condition in which enteral nutrition could be started. In this case, propofol was apparently more suitable than thiamylal to manage a patient with tetanic convulsion.

Aged↗
PubMed1995

Effect of anaesthetic agents on the phagocytic function of human polymorphonuclear leukocytes through analysis with a phagocytic plaque method.

We examined the effects of the intravenous anaesthetic agents, thiamylal and ketamine, on the phagocytic function of polymorphonuclear leukocytes (PMN) in heparinized peripheral blood from healthy individuals using the phagocytic plaque method. Subclinical doses of thiamylal caused enhancement of the phagocytic activity of PMN and super-clinical doses of thiamylal inhibited phagocytic activity of PMN. Ketamine did not adversely affect phagocytic function at relevant therapeutic concentrations. The results presented in this manuscript indicate the phagocytic plaque method can provide a quantitative assessment of the phagocytic function of leukocytes. This method may prove useful in determining whether anaesthetic agents and other drugs adversely affect leukocyte function and hence help prevent the increased susceptibility to infection which can occur in anaesthetized patients. Conversely, the phagocytic plaque method may prove useful in the search for immune-enhancing drugs.

Adult↗
PubMed1994

Haemodynamic and EEG changes during rapid-sequence induction of anaesthesia.

The relationship between the changes in haemodynamic function and the electroencephalogram (EEG) during rapid-sequence induction of anaesthesia was studied in 15 ASA I patients. Anaesthesia was induced with a bolus thiamylal (5 mg.kg-1 iv) followed by succinylcholine (1 mg.kg-1). Tracheal intubation was attempted one minute after the injection of succinylcholine. The EEG was monitored by a computerized aperiodic analysis device, the Lifescan (Neurometrics, San Diego, CA) using the activity edge (AE) to detect brain electrical activity. After induction of anaesthesia, systolic blood pressure (sBP) decreased by 11% from the baseline value, and the AE decreased from 13.0 Hz to 3.4 Hz. Following tracheal intubation, the sBP increased from the post-induction values by 44% (P < 0.05), and the AE increased to 13.1 Hz (P < 0.05) simultaneously. In conclusion, rapid-sequence induction using thiamylal (5 mg.kg-1) caused depression in brain activity as assessed by AE, while laryngoscopy and tracheal intubation caused an increase in activity. This indicates that this dose of thiamylal for rapid-sequence induction may not be sufficient to sustain an adequate anaesthetic level and blunt the haemodynamic responses to intubation.

Adult↗
PubMed2005

A study of the in vitro interaction between lidocaine and premedications using human liver microsomes.

OBJECTIVE: To investigate potential interactions between lidocaine (lignocaine) metabolism and premedication drugs, i.e. psychotropic and antianxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing neuromuscular blocking agents (vecuronium, pancuronium and suxamethonium), an antihypertensive agent (clonidine) and an H2-receptor blocking agent (cimetidine) using human liver microsomes in vitro. METHODS: The interaction effects between lidocaine and premedication were examined using human liver microsomal preparations and monitored for enzyme activity. The lidocaine and its main metabolite (monoethylglycinexylide) were measured by HPLC/UV. RESULTS: Lidocaine metabolism was non-competitively inhibited by midazolam (Ki = 77.6 microM). Thiamylal was a competitive inhibitor of lidocaine metabolism (Ki = 885 microM). Cimethidine, pancuronium and vecuronium weakly inhibited lidocaine metabolism in a concentration-depend manner over the therapeutic range in human liver microsomes. On the contrary, suxamethonium, pentobarbital and clonidine did not inhibit lidocaine metabolism over the therapeutic range in human liver microsomes. CONCLUSION: These results show that the interactions between lidocaine and midazolam and thiamylal are of potential toxicological and clinical significance.

Animals↗
PubMed1992

Differential sensitivity of diabetic rat papillary muscles to negative inotropic effects of oxybarbiturates versus thiobarbiturates.

The negative inotropic effects of oxybarbiturates and thiobarbiturates were examined in papillary muscles isolated from streptozotocin-induced diabetic rats and in papillary muscles from age-matched control rats. The muscles from diabetic rats exhibited less negative inotropic responses to pentobarbital and secobarbital than the muscles from control rats. Conversely, the negative inotropic responses to thiopental and thiamylal were significantly enhanced in diabetic muscles. Differences in sensitivity to pentobarbital between control and diabetic muscles became less marked by treatment with ouabain or by lowering [Na+]o. Enhancement of the negative inotropic effect of thiamylal observed in diabetic muscles remained unchanged with these treatments. In both control and diabetic muscles, the negative inotropic effect of pentobarbital was completely reversed by increasing [Ca2+]o, but the effect of thiamylal was only partially reversed. These results suggest a difference in mechanism of action involved in establishment of the negative inotropic effects of oxybarbiturates vs thiobarbiturates. Oxybarbiturates appear to exclusively reduce the influx of extracellular Ca2+, whereas thiobarbiturates appear to affect Ca2+ movements at the Ca2+ storage sites in addition to the Ca2+ influx inhibition.

Animals↗
PubMed1999

[Changes in ionized magnesium concentrations during general anesthesia].

The change in ionized magnesium (Mg) was investigated during isoflurane-nitrous oxide-oxygen anesthesia. The patients were divided into two groups by induction method of anesthesia. Group 1 was induced with thiamylal 4 mg.kg-1 and Group 2 was induced with ketamine 1 mg.kg-1. The ionized Mg concentration was recorded by NOVA 8 analyzer and observed during anesthesia. We also recorded the serum concentration of total Mg after administration of thiamylal. During induction of anesthesia and surgery, ionized Mg concentration decreased significantly in both groups. The ionized Mg concentration after administration of thiamylal was significantly lower than that after administration of ketamine. The serum total Mg concentration did not decrease throughout the anesthesia course. The ionized calcium concentration decreased, but the concentration of Na and K remained essentially unchanged. We conclude, therefore, that ionized Mg concentration decreases during surgery under general anesthesia, in part, possibly by the effect of anesthetic agent on the cell membrane itself.

Adult↗
PubMed1991

The cardiopulmonary and metabolic effects of hypoxia during acute adrenocortical suppression by etomidate in the dog.

Cortisol is secreted as part of the stress response and has been shown to be potentially beneficial to protect against acute stress. Etomidate specifically suppresses endogenous cortisol production. The author studied cardiopulmonary and metabolic effects of hypoxia in dogs during acute adrenocortical suppression by etomidate. Six chronically tracheotomized dogs were induced with either etomidate or thiamylal. Spontaneous ventilation with constant enflurane concentration was maintained. Two hours after induction of anesthesia, isocarbic hypoxia was induced for 20 minutes. Cardiopulmonary and metabolic variables were recorded at specific intervals. The exact sequence was repeated after 1 hour. Cortisol was measured before, during the experiment, and 24 hours later. The experimental protocol was repeated 6 weeks later on the same dog using the other induction agent (thiamylal group versus etomidate group). Two-factor analysis of variance with contrasts tests was used for statistical analysis. The thiamylal group had a significant decrease in minute ventilation, respiratory rate, partial pressure of oxygen in arterial blood, with increases in partial pressure of carbon dioxide in arterial blood, heart rate and cortisol as compared to the etomidate group. Cardiopulmonary and metabolic responses to hypoxia were comparable in both groups. Therefore, acute suppression of cortisol secretion by etomidate did not adversely alter the responses to hypoxia under enflurane anesthesia in dogs.

Adrenal Cortex↗
PubMed1990

[Midazolam for rapid sequence induction].

We compared midazolam 0.2 mg.kg-1 and fentanyl 50 micrograms with thiamylal 4 mg.kg-1 for rapid sequence induction. We could use midazolam safely in patients with bronchial asthma or drug allergy. There was no difference in time from the beginning of induction to intubation between midazolam treated group and thiamylal treated group. Changes in systolic as well as diastolic blood pressure and heart rate during 2 hours from intubation were smaller in midazolam treated group than in thiamylal treated group. In midazolam treated group, no arrhythmias were observed at the time of intubation. We could reduce the amount of anesthetics in midazolam treated group during 2 hours from intubation. From the results mentioned above, we conclude that midazolam is a useful agent for rapid sequence induction.

Adult↗
PubMed1990

Potency of rapidly acting barbiturates in dogs, using inhibition of the laryngeal reflex as the end point.

Thiopental, thiamylal, and methohexital were administered to 30 dogs to determine equipotent doses necessary to inhibit laryngeal reflexes. The doses studied were 7.1, 10.0, 14.1, 20.0, and 28.3 mg of thiopental/kg of body weight; 5.7, 8.0, 11.3, 16.0, and 22.6 mg of thiamylal/kg; and 3.5, 5.0, 7.1, 10.0, and 14.1 mg of methohexital/kg. At 1, 2.5, 5, and 10 minutes after injection, the presence or absence of the laryngoscopic reflex, pedal reflex, and jaw tone were recorded. The times for return of each reflex, as well as the ability to walk 10 steps without assistance, were also recorded. Using the method of least squares, a probit analysis was performed on the quantal responses at 1 minute. The effective dose in 50% of the population for the laryngoscopic reflex was chosen as the end point for intubation, and the computed doses necessary to achieve this end point were 19.4 mg of thiopental/kg, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg. When potencies of the drugs were compared with that of thiopental (1), thiamylal was found to be equipotent (1.06) and methohexital twice as potent (2.0). At the accepted clinical dose, recovery times for thiopental (71.1 +/- 7.2 minutes) and thiamylal (75.3 +/- 7.7 minutes) were similar, and twice that for methohexital (33.9 +/- 4.6 minutes).

Animals↗
PubMed1990

Cardiovascular and respiratory effects of three rapidly acting barbiturates in dogs.

The cardiovascular and respiratory effects of 3 rapidly acting barbiturates, thiopental sodium, thiamylal sodium, and methohexital sodium, were studied in dogs from completion of injection until 12.5 minutes after injection. The doses administered were 19.4 mg of thiopental/kg of body weight, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg, which were chosen as equipotent doses necessary to inhibit the laryngoscopic reflex in 50% of the population. To determine the cardiovascular and respiratory effects for each drug, the values at each measurement time following injection were compared with baseline values (T0). At the 15- and 30-second measurement times following thiopental administration, stroke volume (SV) decreased; heart rate (HR), left atrial pressure, and mean pulmonary arterial pressure increased; and cardiac index (CI), myocardial contractility, and systemic and pulmonary vascular resistances were not different from baseline values. Mean arterial pressure (MAP) was not different from the baseline value at 15 seconds, but was increased from 30 seconds to 2 minutes. All values except HR had returned to baseline values by 7.5 minutes. At all measurement times, arterial oxygen tension and arterial pH were decreased, and arterial carbon dioxide tension increased from baseline values. Although the cardiovascular and respiratory changes following administration of thiamylal and methohexital were similar to those described for thiopental, some differences were found. Following thiamylal administration, systemic vascular resistance increased at 1 minute, pulmonary vascular resistance increased at 1 and 2 minutes, and myocardial contractility increased at 1 and 2 minutes. Following methohexital administration, MAP decreased at 15 seconds, and SV decreased at all measurement times.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

[Anesthesia combined with profound hypothermia using cardiopulmonary bypass for clipping of giant basilar artery aneurysm].

A 52 year-old female was scheduled for clipping of giant basilar artery aneurysm. This operation needed temporary clipping of the basilar artery for 30-40 minutes, and preoperative examination suggested that some regions would become ischemic by temporary clipping. Therefore profound hypothermia using cardiopulmonary bypass (CPB) and thiamylal loading were planned to prevent cerebral damage during the operation. Anesthesia was induced with thiamylal, fentanyl, and isoflurane in nitrous oxide and oxygen. Following administration of vecuronium, trachea was intubated. Two hours after the start of surgery, thiamylal was titrated to obtain EEG patterns of burst-suppression before CPB and the infusion was continued until CPB was discontinued. With burst-suppression present, CPB was instituted. Hypothermia below 20 degrees C at pulmonary artery temperature was maintained until the aneurysm was clipped and bleeding from the operating site was controlled. Cooling and rewarming by CPB were carried out with ease and uneventfully. The patient had no neurological complications postoperatively.

Basilar Artery↗
PubMed1989

[Comparative effects of inhalation anesthetics on atrioventricular conduction with and without calcium entry blockers].

Calcium entry blockers have been used during general anesthesia in order to control hypertension and tachyarrhythmias. It is well known that both calcium entry blockers (CEBs) and inhalation anesthetics have depressant effects on atrioventricular (AV) conduction and sinus automaticity. Therefore, this study was designed to evaluate combined effects of either halothane, enflurane, isoflurane, or sevoflurane and CEBs (verapamil, diltiazem, or nifedipine) on AV conduction. The following 3 sets of experiments were performed using 90 mongrel dogs anesthetized with ketamine 100-150 mg im, thiamylal 25 mg/kg iv and nitrous-oxide with 50% oxygen. Experiment 1: to evaluate the effects of ketamine and thiamylal on AV conduction. Experiment 2: to evaluate drug interactions of halothane with CEBs. Experiment 3: to evaluate the combined effects of four different inhalation anesthetics at equipotent concentrations (0.8% halothane, 1.6% enflurane, 1.2% isoflurane, and 1.7% sevoflurane) and verapamil. The following variables were measured utilizing His bundle electrocardiogram: Sinus cycle length (SCL), AV conduction time (AH interval), His Purkinje conduction time (HV interval), effective and functional refractory period of AV node (ERP and FRP). It was confirmed that ketamine im and thiamylal iv used for induction of anesthesia did not change AV conduction time from experiment 1. The combined effects of either verapamil (0.1 mg/kg) or diltiazem (0.15 mg/kg) and 0.8% halothane were additive on AV conduction. Although nifedipine (0.01 mg/kg) did not affect AV conduction, there was the significant prolongation of SCL with halothane compared to without halothane. In experiment 3, 0.8% halothane and 1.6% enflurane were stronger than 1.2% isoflurane and 1.7% sevoflurane concerning inhibitory effects on AV conduction. Verapamil had some deleterious effects in 1.6% halothane or 3.2% enflurane anesthesia because of extreme inhibitory effects on AV conduction and sinus automaticity. In conclusion, caution must be exercised in usage of CEBs if inhalation anesthetics are used in higher concentrations.

Anesthesia, Inhalation↗
PubMed1991

Influence of dopamine on cerebral blood flow, and metabolism for oxygen and glucose under barbiturate administration in cats.

The effect of dopamine during barbiturate therapy was investigated in 29 cats including 5 sham-operated cats. According to Kiersey's classification of electro-encephalographic patterns, physiological variables, cerebral metabolic rates for oxygen and glucose, cerebral blood flow (CBF), and intracranial pressure (ICP), etc. were evaluated in each electro-encephalographic pattern. Oxygen-glucose index was calculated and used as an indicator for aerobic or anaerobic metabolism of glucose. Group 1 (12 cats), to which only thiamylal was administered, maintained aerobic glycolysis due to a parallel reduction of cerebral metabolic rates for oxygen and glucose (about half of the initial value at Kiersey's fifth pattern) in spite of reduction of CBF and mean arterial blood pressure (MABP). Group 2 (12 cats), to which dopamine was administered in addition to thiamylal due to a reduction of MABP, showed anaerobic glycolysis though MABP and CBF were maintained. These findings are ascribed to an increase of cerebral metabolic rate for glucose up to 130% of the initial value though cerebral metabolic rate for oxygen decreased down to half of the initial value: The beneficial effect of barbiturate on cerebral metabolism was reduced by use of dopamine. ICP was reduced in both groups. Our result indicates that administration of extracellular fluid may be preferable for treatment of hypotension during barbiturate therapy than dopamine medication.

Animals↗
PubMed1988

Short-acting barbiturate sedation: effect on arterial pH and PaCO2 in children.

One hundred and fifteen unpremedicated children, induced with thiamylal, a short-acting thiobarbiturate, administered rectally (25 mg.kg-1 body wt) or intravenously (6 mg.kg-1) had arterial pH of 7.36 +/- 0.03 and PaCO2 of 40 +/- 4 mmHg. In 22 children over two years of age, the use of fentanyl (1.2 +/- 0.7 microgram.kg-1) in addition to the thiamylal did not change blood gas data compared to those children over two years receiving only barbiturates (pH 7.36 vs 7.36, PaCO2 41 vs 40 mmHg). Children with cyanotic congenital heart disease showed similar pH and PaCO2 to acyanotic children following administration of the short-acting barbiturate. Thiobarbiturates, given in a titrated fashion under direct observation, have clinically small effects on arterial pH and PaCO2 in paediatric patients.

Administration, Rectal↗