Thiamylal Research Articles

The effects of thiamylyl sodium on the tonic vibration reflex in man

The effects of barbiturate on the toxic vibration reflex (TVR) in man were studied. Motor unit spikes elicited during the TVR were recorded before and after an intravenous injection of thiamylal sodium. Thiamylal sodium at a dose between 1.5 and 5.8 mg/kg depressed the motor unit response to muscle vibration. Analysis using a cross-correlation between vibratory stimuli and motor unit spikes confirmed the previously reported existence of two types of motor unit response, i.e. spikes that are locked and those that are not locked to the vibratory stimuli. In addition, the latter type was more susceptible to the depressant effect of thiamylal than the former type. Some possible explanations for the difference in susceptibility of the two types of motor unit to barbiturate are discussed, placing special emphasis on the probable participation of polysynaptic connections from group Ia afferents to motoneurons in the generation of the human TVR.

脳血管攣縮に対するbarbiturate coma therapy

Barbiturate coma therapy was employed in six patients with subarachnoid hemorrhage of grade III and IV to prevent cerebral infarction due to vasospasm after rupture of a cerebral aneurysm. A thick subarachnoid clot and tight brain were shown on CT scans in all of the patients.Barbiturate coma therapy was begun between one and nine days (mean, 5.5 days) after subarachnoid hemorrhage and continued for 49 to 98 hours (mean, 69.3 hours). It was maintained with a continuous intravenous infusion of between 5 and 10mg/kg/hour of thiamylal sodium to achieve burst suppression on the electroencephalogram.Two patients recovered with no neurological deficits, one patient was left in a persistent vegetative state, and three patients died. One of the patients who died recovered to an alert state after barbiturate coma therapy but died from pulmonary embolism 40 days after the subarachnoid hemorrhage.From a reveiw of these six cases, we consider it appropriate for grade IV patients with increased intracranial pressure to receive barbiturate coma therapy immediately after operation and for grade III patients with increased intracranial pressure to receive it immediately after the onset of delayed neurological deficits due to vasospasm.

Comparative hemodynamic effects of propofol and thiamylal sodium during anesthetic induction for myocardial revascularization

The safety and efficacy of propofol, a new intravenous anesthetic agent, have been demonstrated in healthy patients. Twenty-one patients, ASA III–IV, undergoing elective myocardial revascularization, were randomly chosen to receive either propofol, 2.5 mg/kg, or thiamylal, 4 mg/kg, for the induction of anesthesia. Hemodynamics were recorded at one and three minutes after drug administration during spontaneous respiration. After the addition of halothane and pancuronium with controlled ventilation, measurements were made immediately prior to and one minute after intubation. Five patients were dropped from the study, four due to airway problems and one due to severe hypotension following an induction dose of propofol. Statistics were done using data from the remaining 16 patients, eight in each group. Administration of propofol resulted in significant decreases in mean arterial pressure (MAP), systemic vascular resistance (SVR), and left ventricular stroke work index ILVSWI); as well as an increase in heart rate (HR). These changes were further accentuated by the addition of halothane and pancuronium prior to intubation. Patients in the thiamylal group experienced no significant hemodynamic changes until halothane and pancuronium were added and controlled ventilation was instituted. With these additions, the thiamylal group showed significant decreases in MAP and LVSWI immediately prior to intubation. Both groups experienced significant increases in HR following intubation, but no evidence of myocardial ischemia was seen in either group. All other parameters returned toward control values. Propofol appeared to be safe and effective for the induction of anesthesia in this group of patients, although its hemodynamic effects were greater than those of thiamylal.

Letters to the Editor

Abstract Extract Madam: — Sodium thiamylal* * Biotal, Boehringer Ingelheim (NZ) Ltd., P.O. Box 76-216, Manakau City, Auckland is an ultra-short acting thiobarbiturate anaesthetic. It is specifically indicated for producing anaesthesia in dogs, cats, swine, horses and cattle to accomplish interferences of short duration, for induction of anaesthesia followed by gaseous anaesthetic maintenance and for anaesthesia in major surgery by administration of additional amounts as necessary. I would like to record the successful use of this anaesthetic in goats specifically for the purpose of embryo transfer.

Postural influence on systemic blood pressure in large full-term pregnant bitches during general anesthesia.

Effects of positioning on systemic blood pressure were evaluated in six full-term pregnant golden retriever bitches during general anesthesia. Two positions (dorsal and left lateral recumbency) were examined. Anesthesia was induced with thiamylal sodium and maintained with halothane in oxygen. Direct arterial blood pressures were recorded from the bitches in each position. Effects of positioning for each bitch during general anesthesia were reexamined after the bitch weaned its pups; thus, each bitch served as its own control. Maternal posture had no significant effect (p greater than 0.05) on systemic blood pressure. Pregnancy had no significant effect (p greater than 0.05) on systemic blood pressure. Supine hypotension did not occur in anesthetized large, full-term pregnant bitches. Dorsal recumbency was an acceptable position for cesarean sections performed with the patient under general anesthesia.

チアミラールナトリウムの直腸内投与剤形の検討

Polyethylene glycol (PEG) ointment for rectal application containing thiamylal sodium was prepared for premedication of anesthesia and first-aid of pediatric spasmodic disease. The rate of release of thiamylal sodium ointment base was determined by JP X dissolution test and cylindrical method, and showed the increase in parallel with the mixing ratio of PEG 400. Thiamylal sodium in PEG ointment base stored at 4±1°C was stable for 3 months.As a results of the test on spreadability, penetration, rate of release from base and stability, it was suggested that the suitable mixing ratio of PEG 4000 and PEG 400 was 1: 5. Plasma peak level of thiamylal sodium following rectal administration of ointment appeared more rapidly than that of suppository. It has become feasible to have more rapid anesthetic action of ointment than that of suppository.

Prolonged hyporesponsiveness of airway smooth muscle to histamine following general anesthesia.

The prolonged effect of barbiturates and inhalation anesthesia on airway response to histamine was studied in five groups of dogs. Group B (n = 10), H24 (n = 5), and H72 (n = 5) were anesthetized with sodium thiamylal (B) or halothane and N2O (H24, H72) for 3 h, during which a dose-response curve to histamine was obtained. The animals were then allowed to recover; 24 h (B and H24) or 72 h later, the animals were killed and an in vitro dose-response curve to histamine was obtained on a tracheal smooth muscle (TSM) specimen. Group C (n = 5), the control group, had no prolonged exposure to anesthesia. The dogs were immediately killed and the in vitro histamine response of the TSM was measured. The results (mean +/- SE) showed that the smooth muscle contractile properties (i.e., the maximum contraction to electrical field stimulation) were comparable in all four groups: 111 +/- 12 g (B); 168 +/- 23 g (H24); 106 +/- 32 g (H72); and 107 +/- 31 g (C). The maximum response (mean +/- SE) to histamine (as % of maximum electrical contraction) was: 15 +/- 6% (B), 30 +/- 9% (H24), 32 +/- 12% (H72), and 50 +/- 8% (C). Statistical analysis of the data showed that the histamine response of Group B and Group H24 was significantly decreased compared to Group C (P less than 0.01 and less than 0.05, respectively); in Group H72 the results were not significantly different from Group C (0.1 greater than P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetic Management of Equine Head Trauma A Case Report

A fractured frontal bone in an 8‐year‐old Arabian gelding was repaired surgically. The horse exhibited no detectable neurologic deficits before surgery. Anesthesia was induced with a combination of guaifenesin and sodium thiamylal and maintained on halothane in oxygen. Postoperatively, the neurologic status of the horse deteriorated, and it died. On postmortem examination, intracranial hemorrhage accompanied by pressure‐induced malacia of the adjacent brain parenchyma was discovered. The hemorrhage was not associated with the surgical site. The authors hypothesize that increased intracranial pressure occurred in the perioperative period.

Pharmacokinetics of pentobarbital and thiamylal as combined anesthetics in sheep.

This study was performed to investigate the possible mechanisms underlying prolongation of anesthesia times in sheep caused by the sequential administration of thiamylal and pentobarbital. Sodium thiamylal was injected as an intravenous bolus dose (13.2 mg/kg) followed in 7 min by sodium pentobarbital (14.3 mg/kg) by the same route to seven sheep. Separate studies were conducted for each of the two drugs administered separately to the same animals at the same doses. Mean anesthesia times (to the return of the palpebral reflex) were 7.89 min (thiamylal), 5.39 min (pentobarbital) and 34.1 min (the sequential combination). The kinetic parameters Vd(area), Vd(ss), t 1/2 beta, and ClB for either drug were not affected by the other when given in combination. The t 1/2 alpha was shorter, and the Vc was smaller, for pentobarbital when administered with thiamylal, while there were no changes in thiamylal disposition for the combination regimen. Computer-generated curves, associated with the two-compartment open model showing the fraction of dose in each compartment as a function of time, illustrated that pentobarbital rapidly achieved higher concentrations in the peripheral compartment after prior thiamylal administration. Protein-binding studies showed that this could not be attributed to displacement of pentobarbital from plasma albumin by thiamylal. Calculation of total and free drug concentrations at the time of awakening showed that, when the drugs were combined, the concentration of each drug was less than half of that observed at awakening when they were studied separately. It can be concluded that the prolonged sleeping times associated with the sequential combination of the two agents were not due to an alteration in kinetic parameters of either drug caused by the other, but rather to an additive effect of the subanesthetic concentrations of the two drugs when combined. The fact that sleeping times were supra-additive is attributed to a shift of awakening time from the distribution (alpha) phase, when given independently, to the elimination (beta) phase when administered in combination.

Effect of thiamylal and diazepam on release of myoglobin and creatine phosphokinase by succinylcholine chloride during halothane anesthesia.

The effects of thiamylal and diazepam on the release of myoglobin and creatine phosphokinase following the administration of succinylcholine chloride during halothane anesthesia were studied. Thirty patients receiving halothane anesthesia were divided into three groups. In Group I, 1.5-2 mg/kg of thiamylal were given intravenously as pretreatment before the injection of succinylcholine chloride. In Group II, 0.3 mg/kg of diazepam were given and, in Group III, only succinylcholine chloride was injected. A significant increase in the serum myoglobin and creatine phosphokinase levels was observed in all groups. However, the values in Group I were significantly lower than those in Groups II and III and a significant difference was not detected between Group II and III. Our results indicate that thiamylal has a considerable inhibitory effect on the release of myoglobin and creatine phosphokinase from the muscle following the administration of succinylcholine chloride.

Local vasoactivity of oxygen and carbon dioxide in the right coronary circulation of the dog and pig.

1. Eight mongrel dogs were anaesthetized with sodium thiamylal and chloralose-urethane, ventilated, vagotomized and heparinized. Five Poland-China pigs were anaesthetized with sodium thiamylal and nitrous oxide, ventilated, vagotomized and heparinized. 2. Extracorporeal perfusion of the right coronary artery at constant pressure (100 mmHg) was instituted. A lung from a donor animal was interposed in the coronary perfusion circuit to effect changes in CO2 and O2 tensions in the coronary arterial blood while systemic blood gases were maintained at normal levels. 3. Local hypoxia (PO2 range 17-22 mmHg) produced a 25-75% decrease in coronary vascular resistance (P less than 0.05) and a 0-24% (not significant) decrease in right ventricular dP/dt. 4. Local changes in PCO2 over the range 8-105 mmHg were associated with a 17-58% decrease in coronary vascular resistance (P less than 0.05), a 19-24% decrease in right ventricular dP/dt (P less than 0.05) with no change in right ventricular end-diastolic pressure, and a 1-18% (not significant) decrease in heart rate. 5. These studies suggest that local decreases in O2 or increases in CO2 tensions produce decreases in right coronary vascular resistance that are in the opposite direction to those that would be expected from the observed changes in heart rate and contractility (two primary determinants of myocardial oxygen consumption). 6. These data support the hypothesis that CO2 and O2 are locally vasoactive in the coronary circulation.

Prolactin secretion after hypophysial stalk transection in pigs.

Hypothalamic regulation PRL secretion was investigated in 13 7-month-old Yorkshire gilts by comparing the effects of hypophysial stalk transection and sham operation. Ovariectomized gilts were fitted with an indwelling cannula in the anterior vena cava to determine sequential serum profiles of PRL secretion before, during, and 190 h after cranial surgery. A nylon disc was inserted between severed ends of the hypophysial stalk to prevent vascular and tissue regeneration; sham operations included all surgical procedures with exception of stalk transection and insertion of the disc. During a preoperative period of 120 min, PRL concentrations in peripheral serum remained consistently low [2.3 +/- 0.3 ng/ml (mean +/- SEM)] in all gilts. During 105 min of anesthesia (induced by thiamylal sodium and maintained by halothane and oxygen), PRL increased (8.2 +/- 1.9 ng/ml) in all gilts. Peak PRL values averaged 10.7 ng/ml at hypophysial stalk transection or sham operation and then declined steadily in both groups during the last 105 min of surgery. PRL remained elevated (P less than 0.002) in hypophysial stalk-transected gilts compared with sham-operated controls throughout a postoperative period from 6-190 h (3.7 +/- 0.4 vs. 1.9 +/- 0.2 ng/ml). These results indicate that basal secretion of PRL in the pig is inhibited by the hypothalamus.

Antianalgesic action of thiamylal sodium in cats.

The effects of thiamylal on the nociceptor-driven neural activity in the spinal cord were studied in decerebrate, non-anesthetized cats. Noxious stimulation was induced by the injection of bradykinin into the femoral artery and the neutral response in the lateral funiculus was measured by the multi-unit activity technique. The effects of thiamylal on the bradykinin-induced response were compared before and after the spinal cord transection, above the recording site. Thiamylal, 5 mg/kg i.v., potentiated the response significantly before the cord transection and depressed it after the transection. These findings indicate that the antianalgesic action of thiamylal is induced at the spinal cord level: although this anesthetic agent does have a direct intraspinal depressant action, the multisynaptic neural network of the supraspinal pain inhibition system is more susceptible to the actions of anesthetics, and the depression of this descending system by thiamylal results in a release of spinal cord nociceptive neural mechanisms from the supraspinal control.

Comparison of multigated radionuclide angiography with ultrasonic sonomicrometry over a wide range of ventricular function in the conscious dog

This study compared the noninvasive assessment of left ventricular function with radionuclide angiography with that obtained with ultrasonic sonomicrometry. Left ventricular ejection fraction and rate of ventricular ejection (dV/dt) were measured with both techniques over a wide range of ventricular function. Six dogs were prepared with epicardlal crystals across the major and minor axes of the left ventricle, paired transmural wall thickness crystals and a left ventricular catheter. The animals were studied while awake after they had recovered from operation. Left ventricular volume was calculated from the ultrasonic sonomicrometric dimension measurements and the equation for a prolate ellipsoid; dV/dt was calculated from the stroke volume and ejection time. Radionuclide angiograms were performed using technetium-99m-labeled red blood cells and an Anger camera with a converging collimator interfaced to a computer programmed for multigated acquisition. A wide range of ventricular function was produced with sequential infusion of isoproterenol, propranolol, phenylepnrine and sodium thiamylal. Ejection fraction and dV/dt were measured simultaneously during each intervention using the time-activity curves of the multigated radionuclide anglogram and ultrasonic sonomicrometric dimensions. Regression analyses demonstrated a close correlation between the simultaneous measurements of ejection fraction (r values ranged from 0.95 to 0.99) and dV/dt (r values ranged from 0.87 to 0.99). these data indicate that noninvasive multigated radionuclide angiography accurately assesses changes in ejection fraction and dV/dt over a wide range of ventricular function.

Characteristics of protein binding of Thiobarbiturates and 6-n-propyl-2-thiouracil.

To investigate the protein binding characteristics of thiamylal (TA), thiopental (TP) and 6-n-propyl-2-thiouracil (PTU), the effects of pH, ionic strength and temperature on the binding of these three drugs were compared by equilibrium dialysis. The bindings between each of the three drugs and bovine serum albumin (BSA) were similarly dependent on pH. However, the binding constants of TA and TP at pH 7.4 were scarcely influenced by changes of the ionic strength made by the addition of KCl or K2SO4, while that of PTU decreased with increase of the ionic strength. On the basis of these results and the considerable changes in the pKa of bound PTU (previous paper), it is possible that the binding of PTU involves a larger contribution from the interaction with the charged region on BSA than those of TA and TP. A thermodynamic study showed major contributions of ΔS° in the cases of TA and TP and of ΔH° in the case of PTU to ΔG°, suggesting that the binding sites of TA and TP might be different from those of PTU. The pH dependency of binding was also studied by fluorometric titration employing 8-anilinonaphthalene-1-sulfonate (ANS) as an indicator. The displacement ratios of TA and TP increased with increase of pH, in accord with the results of equilibrium dialysis, but that of PTU was only slightly dependent on pH.

Differential depression by apomorphine of the dorsal root potentials spreading caudally and cranially in the cat spinal cord.

The effect of apomorphine on bilateral dorsal root potentials (DRPs) spreading caudally and cranially along three segments of the lower spinal cord was studied in spinal cats anaesthetized with thiamylal sodium. The DRPs were produced by single impulses at 4 times the threshold strength. Apomorphine in a dose of 5 mg/kg, i.v., depressed ipsilateral DRPs spreading caudally to 77% of their initial amplitude and the period of depression was 50 min. Depression of DRPs spreading cranially was significantly greater (maximum reduction to 59%) and lasted about 60 min. Contralateral DRPs spreading cranially were also more depressed than those spreading caudally. These effects were not due to differences in the level of the spinal cord segments investigated. Increase in strength of stimulation to 40 times threshold did not significantly change the depression of DRPs produced by apomorphine. Depression of DRPs depended on the dose of apomorphine. Pimozide and haloperidol blocked the apomorphine-induced depression of the DRPs. It is suggested that differences in the depression of the DRPs spreading caudally and cranially result from different numbers of dopaminergic neurons terminating on interneurons transmitting depolarization cranially or caudally, respectively.

CLINICAL AND HEMATOLOGICAL FINDINGS DURING ELECTROACUPUNCTURAL ANALGESIA (EAA) IN THE DOG

Six clinically healthy mongrels were used repeatedly in the following experiments.(A) Experiments of gradual induction of EAA on bilateral Sp-6 (G.I, experiments) : Load voltage was increased up to 6-7 Vp-p gradually within 60 min., and thereafter maintained for 40 min. (EAA: 5 cases, Control: 5 cases) .(B) Experiments of rapid induction of EAA on bilateral Sp-6 (R.I. experiments) : Soon after i.v, injection of thiamylal sodium 12.5 mg/kg, b.w., load voltage was increased up to 15 Vp-p within 2 min., and thereafter maintained for 60 min. (EAA: 6 cases, Control: cases) . Clinical and hematological observations were performed periodically.Results: (A) G.I. experiments1) During the induction stage dogs were excited, while they were quiet during the maintenance stage.2) Body temperature (T), pulse rate (P) and respiration rate (R) increased accompanying with the increace of load voltage, and decreased gradually during the maintenance stage.3) WBC and neutrophil (%) increased gradually.4) Plasma glucose was elevated during the induction stage, and thereafter reduced gradually.5) No distinct changes were shown in Ht values, total serum protein (TP), plasma urea-N and total cholesterol.Results: (B) R.I. experiments1) Dogs were quiet or drowsy throughout the experiment.2) In the early stage of induction, reduction of T and increase of P were observed, and thereafter T and P returned to normal gradually.3) R showed no remarkable changes.4) WBC and neutrophil (%) increased gradually.5) Plasma glucose showed transient elevation.6) No distinct changes were shown in the levels of Ht, TP, urea-N and total cholesterol.These results supported the authers' view that EAA with premedication of thiamylal sodium was recommended.

Influence of Thiamylal Sodium on Cardiac Function

Influence of Thiamylal Sodium on Cardiac Function

Effect of the Thiamylal Sodium on the Cardiac Function

Effect of the Thiamylal Sodium on the Cardiac Function

Inhibition by six somatostatin analogs of plasma growth hormone levels stimulated by thiamylal and morphine in the rat

Administration of sodium thiamylal (50 mg/kg i.p.) and morphine (3 mg/animal s.c.) leads to high plasma levels of growth hormone (GH) with a maximum measured approximately 30 min after injection. When the same dose of morphine is administered 60 and 120 min later and small additional doses of thiamylal are injected to maintain the animals deeply anesthetized, constant high levels of plasma GH are maintained up to the last interval studied (3 h). This in vivo model has been used to evaluate the potency and duration of action of somatostatin and of six of its analogs by serial blood sampling of animals bearing a cannula inserted into the right superior vena cava. A significant inhibitory effect of somatostatin (45% inhibition) is observed 15 min after a s.c. injection of 1 μg of the pcptide while a near maximal effect (90–95% inhibition) is found at a dose of 25 μg. Both the degree of inhibition and duration of action of somatoslatin are dose-dependent. Inhibitory activities equivalent to 1–250 Mg of somatostatin can be measured with the model described. [Tyr 1] somatostatin, [D-Ala 1] somatostatin, [ N-acetyl-Cys 3] somatostatin and [ N-benzoy 1-Cys 3] somatostatin have activities indistinguishable from somatostatin itself while [D-Lys 4] somatostatin and [des-amino 1, des-carboxy 14]somato statin have approximately 10% the activity of the natural hypothalamic peptide. This in vivo model offers advantageous characteristics of precision and reproducibility for the evaluation of potency of inhibitors of GH release.