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Thiopental or etomidate for rapid sequence induction with rocuronium.

We have assessed the effect of the choice of i.v. induction agent on intubation conditions, 60 s after administration of rocuronium 0.6 mg kg-1. We studied 60 adult patients, allocated randomly to one of two groups. Anaesthesia was induced with alfentanil 10 micrograms kg-1 followed by thiopental 5 mg kg-1 (AT-R group; n = 30) or etomidate 0.3 mg kg-1 (AE-R group; n = 30). Both groups received rocuronium 0.6 mg kg-1. Laryngoscopy was started 60 s later and intubation conditions were evaluated according to a standard score, which considered ease of laryngoscopy, condition of the vocal cords and reaction to intubation. In the AT-R group, overall intubation conditions were scored as excellent in 20 patients, good in nine and fair in the remaining patient. In the AE-R group, overall intubating conditions were excellent in 24 and good in six patients. The difference between the two groups was not significant. Of the three components of the intubation score assessed, response to intubation stimulus was significantly less pronounced in group AE-R compared with group AT-R (P < 0.05): group AE-R, no reaction in 24 patients, slight diaphragmatic movement in five and mild coughing in one patient; group AT-R, no reaction in 13, slight diaphragmatic movement in 14, mild coughing in two and severe coughing in one patient. We conclude that etomidate as part of an induction regimen containing alfentanil and rocuronium attenuated the reaction to intubation to a greater extent than thiopental.

Adolescent↗

Effects of etomidate, propofol and thiopental anaesthesia on arteriolar tone in the rat diaphragm.

We have assessed, by intravital microscopy in rats, the effects of different anaesthetics on diaphragmatic arteriolar diameter. Rats were anaesthetized with etomidate, propofol or thiopental (groups E, P and T, respectively) and the diameters of the arterioles were measured sequentially at baseline and after topical application of either mefenamic acid (MA, 20 mumol litre-1) or N omega-nitro-L-arginine (NNA, 300 mumol litre-1), inhibitors of prostaglandins and nitric oxide, respectively. In group E, baseline arteriolar diameters were significantly higher than those in the two other groups (P < 0.01). MA and NNA induced significant constriction in the three groups (P < 0.001). However, whereas constriction induced by NNA was similar in the three groups, constriction induced by MA was significantly higher in group E compared with groups P and T (P < 0.05). We conclude that diaphragmatic arteriolar diameters in rats were greater during etomidate than during thiopental or propofol anaesthesia. This phenomenon may be mediated by prostaglandins.

Anesthetics, Intravenous↗

Recovery after halothane anaesthesia induced with thiopental, propofol-alfentanil or halothane for day-case adenoidectomy in small children.

We studied recovery from halothane anaesthesia in 93 children, aged 1-3 yr, undergoing day-case adenoidectomy. Children were allocated randomly to receive thiopental 5 mg kg-1 (group TH), alfentanil 10 micrograms kg-1 and propofol 3 mg kg-1 (group PAH) or 5% halothane (group HH) for induction of anaesthesia. In group TH, tracheal intubation was facilitated with succinylcholine (suxamethonium) 1.5 mg kg-1. In groups PAH and HH, tracheal intubation was performed without neuromuscular block, and succinylcholine was used only if required. Anaesthesia was maintained with 1-3% halothane during spontaneous respiration. Times to achieving predetermined recovery end-points were recorded. Quality of recovery was assessed using a score of 1-9 (best to worst) for sedation, crying, restlessness and agitation. A postoperative questionnaire was used to determine the well-being of the child at home, 24 h after operation. Emergence from anaesthesia (response to non-painful stimuli) occurred earlier in group HH (mean 9 (SD 6) min) than in groups PAH (13 (6) min, P < 0.01) and TH (18 (14) min, P < 0.01). Sitting up, walking and home readiness were achieved earlier in groups PAH and HH than in group TH (P < 0.05 for each variable). Children in group TH were more sedated during the first 30 min after anaesthesia than those in the two other groups (P < 0.05) while emergence-related delirium was more common in group HH than in group TH (P < 0.01). Well-being at home was similar in all groups. We conclude that induction of halothane anaesthesia with propofol-alfentanil or halothane provided more rapid recovery and earlier discharge than that with thiopental.

Adenoidectomy↗

Repetitive synchronized cyclical oscillations of multisystem parameters subsequent to high-dose thiopental therapy for status epilepticus secondary to herpes encephalitis.

We report a case of status epilepticus secondary to herpes encephalitis, treated with thiopental infusion and mechanical ventilation. The computerized storage and analysis of physiological data led to the detection of repetitive synchronized cyclical oscillations of arterial pressure, heart rate, EEG parameters, peripheral temperature and core temperature. Arterial pressure oscillations have been described in patients who are severely systemically unwell; cardiovascular and brain electrical activity may also oscillate in the presence of raised intracranial pressure. In contrast, this patient had no features of severe systemic illness or of raised intracranial pressure. Our hypothesis is that high-dose thiopental may have been a cause of our findings by producing autonomic dysfunction.

Adolescent↗

Predicted effect compartment concentration of thiopental at loss of eyelash reflex.

We derived the predicted effect compartment concentration of thiopental, at loss of the eyelash reflex, following three different injection regimens. Sixty patients were given thiopental for induction of anaesthesia. Twenty patients received multiple small boluses, 20 patients received a single bolus and 20 patients received an infusion. Computer simulation was then used to derive the effect compartment concentration. The median concentration was not significantly different between the three groups. EC50, derived after combining all three groups was 11.3 microg ml(-1). The EC05-EC95 range was 6.9-18.3 microg ml(-1), suggesting wide inter-individual variation.

Adult↗

Sevoflurane anaesthesia in children after induction of anaesthesia with midazolam and thiopental does not cause epileptiform EEG.

BACKGROUND: Sevoflurane is a methyl ether anaesthetic commonly used for induction and maintenance of general anaesthesia in children. Sevoflurane is a non-irritant and acts quickly so induction is usually calm. However, inhalation induction with high concentrations of sevoflurane can cause convulsion-like movements and seizure-like changes in the electroencephalogram (EEG). Little is known about the EEG during maintenance of anaesthesia with sevoflurane, so we planned a prospective trial of sevoflurane maintenance after i.v. induction with benzodiazepine and barbiturate, which is another common induction technique in children. METHODS: EEG recordings were made before premedication with midazolam (0.1 mg kg(-1) i.v.), during induction of anaesthesia with thiopental (5 mg kg(-1)), and during maintenance with sevoflurane (2% end-tidal concentration in air/oxygen without nitrous oxide) in 30 generally healthy, 3- to 8-year-old children having adenoids removed. Noise-free EEG data of good quality were successfully recorded from all 30 children. RESULTS: Two independent neurophysiologists did not detect epileptiform discharges in any of the recordings. CONCLUSION: Premedication with midazolam, i.v. induction with thiopental and maintenance of anaesthesia with 2% sevoflurane in air does not cause epileptiform EEG patterns in children.

Anesthesia, General↗

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.

Chromatography, Liquid↗

The effects of sustained hyperventilation on regional cerebral blood volume in thiopental-anesthetized rats.

UNLABELLED: Sustained hyperventilation has a time-limited effect on cerebrovascular dynamics. We investigated whether this effect was similar among brain regions by measuring regional cerebral blood volume (CBV) with steady-state susceptibility contrast magnetic resonance imaging during 3 h of hyperventilation. Regional CBV was determined in nine thiopental-anesthetized, mechanically-ventilated rats every 30 min in the dorsoparietal neocortex, the corpus striatum, and the cerebellum. The corpus striatum was the only brain region showing a stable reduction in CBV during the hypocapnic episode (PaCO(2), 24 +/- 3 mm Hg). In contrast, neocortex and, to a lesser extent, cerebellum exhibited a progressive return toward normal values despite continued hypocapnia. No evidence of a rebound in CBV was found on return to normal ventilation in the three brain regions. We conclude that sustained hyperventilation can lead to an uneven change in the reduction of CBV, possibly because of differences of brain vessels in their sensitivity to extracellular pH. Our results in neocortex confirm the transient effect of sustained hyperventilation on cerebral hemodynamics. IMPLICATIONS: Sustained hyperventilation has a transient effect in decreasing cerebral blood volume (CBV). Using susceptibility contrast magnetic resonance imaging in thiopental-anesthetized rats, we found differences between brain regions in their transient CBV response to sustained hyperventilation.

Anesthesia↗

Plasma protein binding of thiopental in patients with impaired renal or hepatic function.

Binding of thiopental to proteins in plasma from healthy, cirrhotic, and uremic subjects was studied using equilibrium dialysis. In plasma from healthy volunteers 28.0 plus or minus 0.9 per cent of thiopental was unbound. In plasma from patients with hepatic disease 53.0 plus or minus 2.1 per cent was unbound, while in patients with renal disease 55.7 plus or minus 1.5 per cent remained unbound. The decreased binding in uremia could not be explained completely by competitive displacement by nitrogenous end products or by hypoalbuminemia, although hypoalbuminemia may account for the decreased binding in cirrhotic patients.

Binding, Competitive↗

Increase in extracellular potassium in the brain during circulatory arrest: effects of hypothermia, lidocaine, and thiopental.

The effect of temperature (37 degrees C, 28 degrees C, and 18 degrees C), 160 mg/kg lidocaine, and 40 mg/kg thiopental on the efflux of cellular potassium in the cerebral cortex during complete global ischemia was examined. Cerebral ischemia was induced in dogs on cardiopulmonary bypass circulation by stopping the pump. Potassium concentration was measured on the brain surface by a valino-mycine-membrane electrode, which in its response corresponded well to an inserted microelectrode. Hypothermia reduced the ischemic potassium efflux rate to about 50 per cent at 28 degrees C, and about 25 per cent at 18 degrees C. At all temperature levels lidocaine caused an additional reduction in the potassium efflux rate of about 50 per cent, probably by reducing membrane ion permeability in accordance with its local anesthetic action. Thiopental had no effect on the potassium efflux during ischemia. This study opens the possibility that lidocaine, like hypothermia, may provide protection of the ischemic brain.

Animals↗

Pentobarbital and thiopental anesthetic interactions with midazolam.

The effects of midazolam-pentobarbital and midazolam-thiopental combinations on the righting reflex were studied in rats. Doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. Interactions between pentobarbital or thiopental and midazolam were found to be synergistic (supra-additive). The degree of synergism was almost identical with both combinations. The ability of barbiturates to increase the affinity of benzodiazepine receptors to midazolam may be the underlying mechanism for the observed synergism.

Anesthesia, General↗

Plasma drug efflux--a new approach to optimization of drug infusion for constant blood concentration of thiopental and methohexital.

Plasma Drug Efflux is a time-varying measure of the rate of loss of drug from the plasma during conditions of constant plasma concentration. Its practical use is to define the parameters required for a programmed infusion to maintain a desired plasma concentration. The method of deriving the Efflux function, which does not depend on conventional pharmacokinetic models, was developed and tested using thiopental and methohexital in a total of 51 unselected surgical patients free of hepatic or renal disease. Throughout a predetermined, known, but arbitrary computer-controlled drug infusion, the rate of which was modified according to patient lean body mass (LBM) and the desired concentration, blood samples were taken and the plasma assayed for either drug by an HPLC method. By dividing the known variable infusion rate at the time of each sampling by the arterial plasma concentration at each time, an estimate of the rate of loss of drug from the plasma at each point, the Plasma Drug Efflux, was obtained. An error correcting iterative process was used with successive groups of patients until the optimum infusion profile was achieved. Only three iteration steps were required to optimize the infusion profile for each drug. The optimized infusion profile for thiopental was 25.35e-.145t + 4.85e-.0148t + 8.8 ml X min-1 X kgLBM-1, and, for methohexital, 22.21e-.092t + 5.09e-.0121t + 15 ml X min-1 X kgLBM-1. It was concluded that the process of optimization under clinical conditions resulted in infusion profiles suitable for establishing and maintaining a designated arterial plasma concentration in adult surgical patients for periods up to 3 h.

Adult↗

Reduction of tonic ribcage muscle activity by anesthesia with thiopental.

Surface electromyograms were recorded from the scalene, sternomastoid, and parasternal intercostal muscles in 16 supine premedicated adult patients before, during, and after the induction of anesthesia with thiopental and after the administration of succinylcholine. Muscle activity was measured as the rectified, integrated signal, and expressed as a percentage of the activity detected during a maximal inspiration. Activity was found in the scalene and sternomastoid muscles of all patients, and in the intercostal muscles of 13. This activity was more commonly tonic, and, at end-expiration, it was 7%, 6%, and 5% of the activity that could be generated by a maximal inspiration, for the scalene, sternomastoid, and intercostal muscles, respectively. In all subjects, this activity was markedly reduced or abolished by the administration of thiopental, to 0.7%, 0.6%, and 0.6%, respectively. There was no tonic activity in these muscles during spontaneous respiration after induction of anesthesia. It is suggested that the reduction of tonic inspiratory activity in these muscles may contribute to the reduction in functional residual capacity associated with anesthesia.

Anesthesia↗

Propofol-nitrous oxide versus thiopental-isoflurane-nitrous oxide for general anesthesia.

One hundred and twenty patients undergoing elective operations were randomly assigned to receive anesthesia with either thiopental, 4 mg/kg-isoflurane, 0.2-3%-nitrous oxide, 60-70% (control) or propofol, 2 mg/kg-propofol infusion, 1-20 mg/min-nitrous oxide, 60-70% (propofol). Although anesthetic conditions were similar during the operation, differences were noted in the recovery characteristics. For non-major (superficial) surgical procedures, the times to awakening, responsiveness, orientation, and ambulation were significantly shorter in the propofol group (4 +/- 3, 5 +/- 4, 6 +/- 4, and 104 +/- 36 min) than in the control group (8 +/- 7, 9 +/- 7, 11 +/- 9, and 142 +/- 61 min, respectively). In addition, less nausea and vomiting (20 vs. 45%) and significantly less psychomotor impairment was noted in the non-major propofol (vs. control) group. Following major abdominal operations, recovery characteristics did not differ between propofol and control groups. Delayed emergence (greater than 20 min), significant psychometric impairment, and a high overall incidence of postoperative side effects (55-60%) were noted in both drug treatment groups. The authors conclude that propofol-nitrous oxide compares favorably to thiopental-isoflurane-nitrous oxide for maintenance of anesthesia during short outpatient procedures. However, for major abdominal operations, propofol anesthesia does not appear to offer any clinically significant advantages over a standard inhalational anesthetic technique.

Adult↗

Induction of anesthesia with small doses of sufentanil or fentanyl: dose versus EEG response, speed of onset, and thiopental requirement.

The purpose of this study was to examine the dose versus EEG response relationship, the speed of onset, and the thiopental requirement for induction of anesthesia with small doses of sufentanil and fentanyl. The power spectrum of the electroencephalogram (EEG) was used to quantify the effect of the opioids. Eight male surgical patients, 52-80 yr old, were randomly divided into eight groups of ten to receive fentanyl, 5, 7, 10, or 13 micrograms/kg, or sufentanil, 0.5, 0.7, 1.0, or 1.3 micrograms/kg. The opioid was given iv over 1 min at a constant rate of infusion. Three to four minutes after the start of the opioid dose, thiopental was given iv in 25 mg increments every 30 s until the patient was unconscious. Power in the 1-3 Hz band reached maximum levels in less than 4 min after the start of opioid administration. At fentanyl doses of 7.0 micrograms/kg or less, or sufentanil doses of 1.0 micrograms/kg or less, the EEG effects did not increase in proportion to the dose of opioid. There was not a significant difference in the maximum power achieved in the 1-3 Hz band for sufentanil, 0.5, 0.7 and 1.0, and fentanyl, 5 and 7 micrograms/kg. Doses of fentanyl, 10 or 13 micrograms/kg, or sufentanil, 1.3 micrograms/kg were substantially more effective; the maximum power increased significantly between 7 and 10 micrograms/kg of fentanyl and 1.0 and 1.3 micrograms/kg of sufentanil (P less than 0.0001). The potency of sufentanil and fentanyl were compared by super-imposing, the dose versus response (power) curves. The potency ratio was 1:8 (sufentanil:fentanyl).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Intracranial volume-pressure relationship following thiopental or etomidate.

A series of infusions of mock cerebrospinal fluid (CSF) was used to determine intracranial volume-pressure relationships in 18 anesthetized dogs. Measures of intracranial volume-pressure relationships included 1) CSF pressure prior to volume infusion (P0), 2) peak CSF pressure (Pp) caused by volume injection, 3) intracranial compliance (C, calculated as the ratio of change of intracranial volume [delta V] to change of CSF pressure [delta P]), 4) the volume-pressure response (VPR, a measure of elastance, calculated as the ratio of delta P to delta V), 5) the pressure volume index (PVI, calculated as the ratio of delta V to log Pp/P0), and 6) estimated intracranial compliance (Ce, calculated from PVI as 0.4343 PVI/P0). Six of the 18 dogs (time controls) were studied during halothane (0.4%, end expired) and nitrous oxide (66%) in oxygen, six dogs were studied prior to and following each of two doses of thiopental (approximate cumulative doses were 10.5 and 25.5 mg/kg), and six dogs were studied prior to and following each of two doses of etomidate (approximate cumulative doses were 1.52 and 3.70 mg/kg). In the time controls P0, Pp, C, VPR, PVI, and Ce were steady throughout the experimental period. Thiopental decreased P0 (by 2-3 +/- 1 cmH2O) and Pp (by 2-4 +/- 2 cmH2O), increased Ce (by 0.02-0.03 +/- 0.01 ml/cmH2O), and did not change C, VPR, or PVI. Etomidate decreased P0 (by 3-4 +/- 1 cmH2O) and Pp (by 4-6 +/- 2 cmH2O), increased Ce (by 0.03-0.04 +/- 0.01 ml/cmH2O) and did not change C, VPR, or PVI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of thiopental, pentobarbital, and ketamine on endothelin-induced constriction of porcine cerebral arteries.

Contractile mechanisms of endothelin, a newly isolated vasoactive substance from endothelium, were evaluated in anterior cerebral arteries (ACA). Furthermore, the effects of thiopental, pentobarbital, ketamine, and diltiazem on the endothelin-induced cerebral vasoconstriction were also studied. Endothelin induced cerebral arterial contractions in concentrations above 3 X 10(-10) M. The median effective concentration (ED50: X10(-9) M) of endothelin was 2.1 +/- 0.7 (n = 6). Endothelin did not elicit contractions in preparations soaked in Ca2(+)-free solution, but addition of 2.5 mM Ca2+ to the baths induced marked contractions. Thiopental and pentobarbital attenuated endothelin-induced contractions at concentrations above 3 X 10(4) M, while ketamine was effective above 10(-3) M. In contrast, diltiazem decreased endothelin-induced vasoconstriction at 10(-6) M. The findings suggest that endothelin may cause contractions of porcine cerebral arteries by influx of Ca2+ through Ca2+ channels. The cerebral vasomotion induced by endothelin, however, does not seem to be influenced by clinical doses of barbiturates and ketamine.

Animals↗

Effects of propofol and thiopental on maternal and fetal cardiovascular and acid-base variables in the pregnant ewe.

BACKGROUND: The effects of propofol on uterine blood flow are not understood well. This is a relatively new agent that is finding increased use for nonobstetric surgical procedures during pregnancy and induction of anesthesia for cesarean section. METHODS: The effects of induction and maintenance of anesthesia with propofol were studied on maternal and fetal cardiovascular and acid-base variables in a chronically instrumented pregnant sheep model. Anesthesia was induced with a 2 mg/kg bolus of propofol and maintained with of one of three continuous infusions: 150, 300, and 450 micrograms.kg-1 x min-1. The control group received thiopental for induction, and anesthesia was maintained with isoflurane. RESULTS: The use of propofol did not adversely affect maternal or fetal mean arterial pressure, heart rate, or base excess, fetal heart rate variability, or uterine blood flow. Uterine blood flow transiently decreased during induction and intubation with thiopental but remained stable during induction with propofol. However, administration of succinylcholine for intubation in the presence of propofol resulted in a transient, but severe, maternal bradycardia. Continuous infusion of 300 micrograms.kg-1.min-1 of propofol appeared to provide satisfactory anesthesia in the ewe. CONCLUSIONS: Assuming the applicability of ovine data to humans, these findings suggest that induction and maintenance of anesthesia with propofol and 50% nitrous oxide in oxygen has no adverse fetal effects but warrants caution because of the potential risk of severe maternal bradycardia during induction of anesthesia using the combination of propofol and succinylcholine.

Acid-Base Equilibrium↗