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The effects of cardiopulmonary bypass on plasma concentrations and protein binding of methohexital and thiopental.

The effects of cardiopulmonary bypass (CPB) on plasma concentrations and protein binding of methohexital and thiopental were studied during continuous infusions in two groups of ten cardiac surgical patients. Patients were administered an infusion regimen designed to produce a stable total plasma concentration at 5 mg/L for methohexital and 10 mg/L for thiopental. Prior to the commencement of CPB the mean (+/-SD) total plasma methohexital concentration was 5.00 +/- 0.69 mg/L. This fell to 3.12 +/- 0.89 mg/L at two minutes after commencement of CPB, and rose to 4.67 +/- 1.11 mg/L by 75 minutes after commencement of CPB. The unbound fraction rose from 27.1 +/- 5.1% to 42.8 +/- 9.2% at five minutes after the start of CPB, and gradually decreased to 32.1 +/- 4.9% by 75 minutes. The unbound concentration (1.37 +/- 0.32 mg/L) was unaffected by the onset of CPB, being 1.51 +/- 0.49 mg/L at 75 minutes after the start of CPB. Thiopental followed a similar pattern to methohexital, with the total plasma thiopental concentration falling from 9.22 +/- 0.73 mg/L to 4.90 +/- 0.83 mg/L at two minutes after commencement of CPB, and rising again to 7.13 +/- 1.03 mg/L 75 minutes later. During the same period the unbound fraction of thiopental rose from 16.1 +/- 2.5% to 30.3 +/- 7.3% five minutes after the start of CPB, and fell gradually to 22.8 +/- 5.8% after 75 minutes. The unbound concentration (1.51 +/- 0.21 mg/L) was again unchanged by the onset of CPB, being 1.71 +/- 0.29 mg/L at 75 minutes. Plasma protein binding of both drugs correlated strongly with plasma albumin concentration, which decreased by 40% during CPB. It is concluded that hemodilution caused the reduction in total drug concentration and protein binding at the onset of CPB, but that the decrease in protein binding counteracted the dilution of unbound drug, resulting in a stable unbound concentration throughout CPB, and that this effect may be common for barbiturates.

Analysis of Variance↗

Evaluation of the thiopental test in epilepsy surgery patients.

One hundred and three patients underwent a thiopental test during a presurgical evaluation for epilepsy surgery. Depth electrodes were implanted bilaterally into the mesial temporal and mesial frontal lobes. Thiopental was infused at 25 mg/30 s for adults and 0.3 mg/kg/20 s in children until loss of corneal reflexes or a total of 1 g. The absence of beta activity on the EEG, and activation of interictal spiking were two parameters monitored at all recording sites. Positive results were correlated with the anatomy of the ictal epileptic foci. Half of the patients produced increased interictal spiking and three-quarters of them showed absence of beta production in at least one lobe. Despite a reasonably high concordance between ictal foci and the two thiopental parameters, both measures yielded a low sensitivity and specificity. This work, as well as that reported in the literature, was unable to confirm the hypothesis that local damage within the temporal lobe was responsible for positive thiopental test results. An alternative hypothesis is proposed that the thalamus may be a distant source of these findings. Irrespective of the mechanism, the thiopental test must be used cautiously in the evaluation for epilepsy surgery.

Electrodes↗

Anesthesia for craniotomy: total intravenous anesthesia with propofol and alfentanil compared to anesthesia with thiopental sodium, isoflurane, fentanyl, and nitrous oxide.

STUDY OBJECTIVE: To compare a total intravenous (IV) anesthetic technique based on propofol and alfentanil with a commonly used anesthetic technique for craniotomy. DESIGN: Open-label, randomized, clinical study. SETTING: Neurosurgical clinic at a university hospital. PATIENTS: Forty patients, aged 18 to 55 years, scheduled for brain tumor surgery. INTERVENTIONS: In 20 patients, anesthesia was induced with fentanyl and thiopental sodium and maintained with fentanyl, dehydrobenzperidol, isoflurane, nitrous oxide (N2O), and a thiopental sodium infusion. Twenty patients were anesthetized with a propofol loading infusion followed by a maintenance infusion at a fixed rate. In addition, alfentanil was administered as a loading bolus, followed by a variable-rate infusion, with additional doses as necessary to maintain hemodynamic stability. MEASUREMENTS AND MAIN RESULTS: A decrease in blood pressure (BP) after induction with thiopental sodium was followed by a significant increase in BP and heart rate (HR) during intubation. BP and HR did not change during the propofol loading infusion. However, the administration of alfentanil was followed by a similar decrease in BP with a return to baseline values during the intubation period. Return of normal orientation (7 +/- 5 minutes vs 27 +/- 23 minutes) and concentration (12 +/- 12 minutes vs 35 +/- 37 minutes) was shorter and more predictable for the propofol-alfentanil-treated patients than for the thiopental sodium patients. Maintenance propofol concentration (nine patients) was between 3 +/- 0.69 micrograms/ml and 3.36 +/- 1.17 micrograms/ml, while the concentration at awakening was 1.09 microgram/ml. Alfentanil concentration at extubation (nine patients) was 79 +/- 34 ng/ml. CONCLUSION: A total IV anesthetic technique with propofol and alfentanil is a valuable alternative to a more commonly used technique based on thiopental sodium, N2O, fentanyl, and isoflurane.

Adult↗

Effect of alfentanil on hypnotic and antinociceptive components of thiopental sodium anesthesia.

STUDY OBJECTIVE: To determine the effects of alfentanil on the hypnotic and antinociceptive components of thiopental sodium anesthesia. DESIGN: Randomized double-blind study. SETTING: Inpatients at a university-affiliated county hospital. PATIENTS: Eighty unpremedicated ASA physical status I or II female patients aged 18 to 60 years, with a weight range of 50 to 90 kg. INTERVENTIONS: Intravenous injection of thiopental sodium in doses ranging from 1.0 mg/kg to 6.0 mg/kg with or without the addition of alfentanil, 0.01 mg/kg. MEASUREMENTS AND MAIN RESULTS: Dose-response curves were determined for the following three endpoints of anesthesia: eye opening in the response to voice command; eye opening in the response to noxious stimulation induced by pressure on the trapezius muscle; and purposeful movement in the response to the same type of noxious stimulation. The addition of alfentanil, 0.01 mg/kg, markedly decreased thiopental ED50 values for all three endpoints: from 2.6 mg/kg to 1.9 mg/kg (p less than 0.02) for eye opening to voice command, from 3.2 mg/kg to 1.9 mg/kg (p less than 0.0005) for eye opening to noxious pressure, and from 4.2 mg/kg to 2.4 mg/kg (p less than 0.0001) for purposeful movement to noxious pressure. The alfentanil-induced increase in thiopental potency for the antinociceptive effect was greater than that for the hypnotic effect (75% vs 36%, p = 0.02). CONCLUSIONS: Alfentanil strengthened both the hypnotic and antinociceptive components of thiopental anesthesia, although to a different degree: the antinociceptive component more so than the hypnotic, possibly because each component of anesthesia has different underlying mechanisms.

Adult↗

Which induction drug for cesarean section? A comparison of thiopental sodium, propofol, and midazolam.

STUDY OBJECTIVE: To determine maternal and neonatal effects of three different induction drugs (thiopental sodium, propofol, and midazolam) for cesarean section. DESIGN: Randomized, double-blind study. SETTING: Inpatient obstetric department at a general hospital. PATIENTS: 90 healthy patients undergoing elective cesarean section with general anesthesia. INTERVENTIONS: 3 groups of 30 patients each receiving thiopental 5 mg/kg, propofol 2.4 mg/kg, or midazolam 0.3 mg/kg for induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Time to induce anesthesia, hemodynamic changes, depth of anesthesia, recovery after anesthesia, placental transfer, and neonatal outcome (Apgar and neurobehavioral examinations) were studied. In the thiopental and midazolam groups, systolic blood pressure and heart rate rose following endotracheal intubation and skin incision (p < 0.001 and p < 0.0025, respectively), while in the propofol group, there was significant hypotension after induction (p < 0.005). Electroencephalographic patterns showed a light depth of anesthesia with propofol and midazolam between anesthesia induction and delivery, confirmed by the presence of clinical signs of light anesthesia in 50% of propofol patients and 43% of midazolam patients. Time to induce anesthesia was longer with midazolam (p < 0.0001). Neonates in the midazolam and propofol groups had lower Apgar and neurobehavioral scores than those in the thiopental group. Umbilical artery to umbilical vein ratios were above 1 in the propofol and midazolam groups. CONCLUSION: Thiopental still remains the first-choice induction drug for cesarean section. The slow induction time with midazolam may put the mother at risk for pulmonary inhalation. A plane of anesthesia that may risk awareness and potential neonatal depression is the main drawback of the two newer induction drugs.

Adult↗

Rapid in vitro elimination of anesthetic doses of thiopental in the isolated guinea pig brain.

Electrophysiological and metabolic activities in brain tissue preparations maintained in vitro may be influenced by the persistent effect of anesthetic drugs utilized during tissue dissection. In order to clarify this issue, we studied elimination kinetics of the barbiturate thiopental from the brain parenchyma in the isolated guinea pig brain maintained in vitro, arterially perfused with a protein-free saline solution [M. de Curtis, G. Biella, C. Buccellati, G. Folco, Simultaneous investigation of the neuronal and vascular compartments in the guinea pig brain isolated in vitro, Brain Res. Protoc. 3 (1998) 21-28]. At the onset of anesthesia induced by a single i.p. injection of 125 mg/kg thiopental, the brain concentration of the drug, measured by high-performance liquid chromatographic assay, was 44.22+/-5.1 mg/L (mean+/-S.E.; n=7). After 30 min of arterial perfusion in vitro with a thiopental-free solution, the cerebral levels of the barbiturate decreased to 2.03+/-0.56 mg/L (n=3), and reached values close to zero within 1 h. No significant changes in thiopental elimination curve were observed when in vitro perfusion rate was either increased or decreased. The study demonstrates that thiopental is rapidly eliminated from the brain tissue with a mono-exponential kinetic. It can be concluded that barbiturate anesthesia utilized during brain dissection is not likely to influence activities recorded from the in vitro isolated brain preparation.

Anesthetics↗

No effect of age on the dose requirement of thiopental in the rat.

With increasing human age (20-80 years), the electroencephalogram (EEG) dose requirement for the intravenous anesthetic thiopental decreases approximately 10% per decade of life. The goal of this study was to compare the dose required to attain isoelectric EEG in young (4-5 month) vs. aged (24-25-month) Fischer 344 rats. One second isoelectricity was found to be an endpoint where minimal cardiorespiratory depression occurred. The effects of age, infusion rate, and repeated administration were examined in nine young and nine old rodents. Thiopental dose requirement increased with increasing infusion rates. Repeated administration at two-day intervals did not demonstrate tolerance to thiopental. No difference in thiopental dose requirement was detected in the young vs. elderly rats. In a separate group of five young and five old rats, thiopental plasma, brain, heart, and CSF concentrations were measured when five seconds of EEG isoelectricity was achieved: no consistent differences were noted. The rat may not be an appropriate model to investigate acute age-related anesthetic effects in humans, because cardiovascular changes with age are dissimilar between species.

Aged↗

Induction of anesthesia by titration of eltanolone compared with thiopental and etomidate for coronary artery bypass grafting.

STUDY OBJECTIVE: To evaluate whether induction of anesthesia with eltanolone in coronary artery bypass graft (CABG) patients is associated with greater hemodynamic stability than either thiopental sodium or etomidate. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 75 ASA physical status III and IV patients scheduled for elective CABG over 18 years of age, with left ventricular ejection fraction over 30%. INTERVENTIONS: The participants were prospectively randomized into three groups, each group consisting of 25 patients. Anesthesia was induced by titration of either eltanolone, thiopental sodium, or etomidate. The end point was "loss of verbal contact." MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables were recorded in the awake state, 2 minutes after induction, after administration of fentanyl 0.01 mg/kg, and 2 and 5 minutes after intubation. After induction of anesthesia, cardiac index (CI) decreased from 2.6 +/- 0.5 to 2.2 +/- 0.5 Lxmin-1xm-2 in the eltanolone group and remained at this value throughout the study period in contrast to the control groups. After fentanyl was given, mean arterial pressure was significantly lower in the case of eltanolone (69 +/- 15 mmHg) compared with thiopental (81 +/- 19 mmHg) and etomidate (84 +/- 18 mmHg). Mean arterial pressure remained significantly lower at the points of measurement after intubation. Two minutes after intubation, CI was likewise significantly lower in the eltanolone group (2.2 +/- 0.4 Lxmin-1xm-2) compared with the thiopental group (2.7 +/- 0.7 Lxmin-1xm-2). CONCLUSIONS: Eltanolone produces more hemodynamic depression compared with etomidate and thiopental when administered in combination with fentanyl 10 micrograms/kg.

Aged↗

Influence of thiopental and propofol on postoperative cognitive recovery in the elderly patient undergoing general anesthesia.

STUDY OBJECTIVE: To assess mental and psychomotor recovery following induction of anesthesia with thiopental or propofol in elderly patients undergoing general anesthesia. DESIGN: Randomized, prospective, double-blind study. SETTING: Large referral hospital. PATIENTS: 40 elderly patients ASA physical status I-III (> 65 years) undergoing abdominopelvic surgery with an estimated surgical time of at least 90 minutes. INTERVENTIONS: All patients received combined epidural-general anesthesia. After establishing a T6 sensory blockade, patients were randomized to receive either thiopental or propofol for induction of general anesthesia. The induction drug was slowly titrated until loss of eyelash reflex was noted. Thereafter, all patients received desflurane (2% to 3% end-tidal) and 70% nitrous oxide (N2O) in oxygen for maintenance of general anesthesia. To facilitate tracheal intubation, intravenous alfentanil 10 micrograms/kg and atracurium 0.4 mg/kg were administered. Perioperative analgesia was maintained with epidural bupivacaine. MEASUREMENTS AND MAIN RESULTS: A digit substitution test (DSST) and shape-sorter test, as well as patient-generated 100-mm visual analog score (VAS; 0 = minimal and 100 = maximal) for anxiety, sleepiness, and coordination, were performed during the preanesthetic interview, on postanesthesia care unit admission, and at 15, 45, 90, and 120 minutes thereafter. To induce loss of consciousness, either thiopental 2.5 +/- 1.0 mg/kg or propofol 1.6 +/- 0.6 mg/kg was administered. The mean anesthetic time was 109 +/- 30 minutes and 114 +/- 38 minutes for the thiopental and propofol groups, respectively. Emergence, extubation, and orientation times, as well as time to follow commands, were unaffected by patient randomization. Similarly, the DSST and shape-sorter tests, in addition to the patient-generated VAS for pain, anxiety, and coordination, were similar among groups. However, irrespective of treatment modality, return to baseline digit substitution and shape-sorter scores were significantly delayed (p < 0.01). CONCLUSION: When compared to thiopental, propofol does not facilitate improved cognitive recovery in geriatric patients undergoing prolonged surgery.

Aged↗

QT interval and QT dispersion during the induction of anaesthesia in patients with subarachnoid haemorrhage: a comparison of thiopental and propofol.

BACKGROUND AND OBJECTIVE: Thiopental prolongs the QT interval more than propofol, and the two induction agents were compared in patients with subarachnoid haemorrhage predisposed to electrocardiographic abnormalities and cardiac dysrhythmias. METHODS: Twenty-nine patients were studied randomly. Anaesthesia was induced with either thiopental or propofol and fentanyl; vecuronium was used as a neuromuscular blocking agent. The electrocardiogram and arterial blood pressure were monitored from before the induction of anaesthesia to 2 min after endotracheal intubation. RESULTS: The median QT interval was at baseline 423 ms in the thiopental group and at 432 ms in the propofol group, and it increased in the thiopental group to 446 ms and decreased in the propofol group to 425 ms (P < 0.01 between groups). After induction and endotracheal intubation, the number of patients with increased QT dispersion was greater in the propofol group (P < 0.05). The incidence of cardiac dysrhythmias was similar in the study groups. CONCLUSIONS: Thiopental and propofol are equally suitable for the induction of anaesthesia in patients with subarachnoid haemorrhage.

Anesthesia, Intravenous↗

The effect of sedation on weaning following coronary artery bypass grafting: propofol versus oxycodone-thiopental.

BACKGROUND: Propofol has been advocated for sedation in intensive care because of superior recovery characteristics. We hypothesised that the use of two totally different sedation methods after coronary artery bypass grafting should result in differences not only in extubation time, but also in breathing pattern and gas exchange during weaning and after extubation. METHODS: Thirty patients participated in this randomised and controlled study. We used propofol infusion and oxycodone-thiopental bolus dosage, titrated to sedation level 4 or 5 according to Ramsey. Weaning was performed using protocol-based pressure support trials. RESULTS: Total (SD) fentanyl dose during operation was 33 (6) microg x kg(-1) for propofol and 34 (6) microg x kg(-1) for oxycodone-thiopental (ns). The target sedation was achieved equally with both methods. The time from admission to intensive care unit to extubation was 494 (100) min for propofol and 521 (98) min for oxycodone-thiopental (ns). Weaning times were 63 (24) min and 112 (63) min in the propofol and oxycodone-thiopental groups, respectively (P<0.05). Breathing frequency increased and tidal volume decreased from weaning to 2 h postextubation. CONCLUSION: Propofol infusion and oxycodone-thiopental bolus dosages, titrated to the same sedation end point, resulted in similar time from admission to extubation, although the weaning period was shorter in the propofol group. In terms of breathing pattern, gas exchange, blood gases and haemodynamics, the methods were similar. Propofol, despite its attractive pharmacological profile, may offer no clinical benefit in short-term sedation after a moderate dose fentanyl anaesthesia in cardiac surgery.

Carbon Dioxide↗

Etomidate and thiopental inhibit platelet function in patients undergoing infrainguinal vascular surgery.

BACKGROUND: Postoperative platelet hyperaggregability following general anesthesia has been reported in patients undergoing major vascular surgery. In contrast, since anesthetic agents inhibited platelet function both in vitro and in vivo, an increased risk for postoperative bleedings due to prolonged platelet dysfunction has been discussed. Nevertheless, data describing platelet-affecting properties of induction agents such as etomidate and thiopental in patients undergoing major vascular surgery are lacking. METHODS: Platelet function was determined at 0, 2, 20, and 200 microg/ml thiopental and at 0, 0.2, 2, 20 microg/ml etomidate in vitro in blood samples drawn from 16 patients suffering from severe occlusive arterial disease. In addition, 30 patients undergoing vascular surgery were investigated before (PRE) and after anesthesia induction (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14), and 2 h after the beginning of surgery (T2). Platelet function was determined according to platelet aggregation, in vitro bleeding time, and flow cytometric measurements. RESULTS: In vitro, P-selectin expression was inhibited by etomidate at 2 and 20 microg/ml (-28% and -38%, respectively) and also by thiopental at 200 microg/ml (-27%). In patients undergoing vascular surgery, anesthesia induction in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and an inhibition of ADP- and collagen-induced platelet aggregation (-30% and -17%, respectively) and of P-selectin expression (-25%) at T0. In the THIO group, only ADP-induced platelet aggregation was affected (-16%). At T2, all parameters had reached PRE level again in both groups. Furthermore, in comparison with the THIO group, operation time was significantly prolonged and transfusion volume was significantly increased in the ETO group. In addition, platelet count and hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1, fibrinogen and antithrombin III and partial thromboplastin time remained unchanged in both groups during the study period. CONCLUSIONS: In the present study, etomidate and, to a minor extent, thiopental offered significant platelet inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher transfusion rates and prolonged operation times. Therefore, anesthetic-related platelet inhibitory properties should be considered when searching for the anesthetic agent of choice, especially in patients with compromised hemostasis and co-existing bleeding disorders.

Aged↗

High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice.

BACKGROUND: Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high dose. This study investigated the effects of flumazenil and midazolam on the hypnotic dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS: Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS: Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the hypnotic dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the hypnotic dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the hypnotic activity of propofol. CONCLUSIONS: These results suggest that the hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.

Anesthetics, Intravenous↗

Evaluation of plasma levels of melatonin after midazolam or sodium thiopental anesthesia in children.

Midazolam and sodium thiopental are two commonly used drugs in anesthesia for minor surgical procedures in children. A relationship exists between benzodiazepines (BNZ), barbiturates and melatonin. Whereas these drugs increase pineal melatonin production, the indoleamine amplifies the effects of both BNZ and barbiturates on the central nervous system (CNS). Our purpose was thus to analyze the plasma levels of melatonin before and during midazolam or sodium thiopental anesthesia in children subjected to ambulatory surgical procedures. Midazolam (0.4 mg/kg) or sodium thiopental (5 mg/kg) were administered i.v. to 33 and 32 children (aged between 2 and 14 yr), respectively, and blood samples were taken before and 5, 10 and 20 min after the drugs were administered. Melatonin was measured in plasma by a commercial radioimmunoassay kit previously standardized in our laboratory. The results showed that neither midazolam nor sodium thiopental anesthesia significantly affected the levels of melatonin studied at anytime. Significant correlations were found comparing the levels of melatonin between the different times studied. These results suggest that midazolam or sodium thiopental did not affect melatonin production by the pineal gland, thus avoiding a possible potentiating effect of the indoleamine on the central effects of these drugs during anesthesia. However, the possibility that changes in melatonin had been masked by the antioxidant role of the neurohormone are discussed.

Adolescent↗

Decreased protein binding and thiopental kinetics.

Thiopental kinetics and protein binding were determined in seven surgical patients with chronic renal failure and a thiopental free fraction of 28.0 +/- 6.5% (SD) and in seven age- and weight-matched normal surgical patients with a thiopental free fraction of 15.7 +/- 2.4%. Thiopental clearance, based upon total plasma concentrations, rose from 3.2 +/- 0.6 ml/kg/min in the normal group to 4.5 +/- 1.1 ml/kg/min in the chronic renal failure group. Volume of distribution at steady state, also based on total drug concentrations, rose from 1.9 +/- 0.5 l/kg in the normal group to 3.0 +/- 1.0 l/kg in the chronic renal failure group. These changes in clearance and volume of distribution at steady state are secondary to changes in free drug distribution and elimination. When kinetics were calculated from free drug concentrations, the intrinsic clearance, unbound volume of distribution at steady state, and free fraction in tissues in the normal and renal failure groups did not differ substantially. These data suggest that the kinetic changes based on total drug concentrations are secondary to changes in free fraction in plasma. In chronic renal failure patients, the underlying rate and extent of thiopental distribution and elimination are much the same as in normal patients.

Blood Proteins↗

Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest.

After restoration of spontaneous circulation and adequate oxygenation, 262 comatose survivors of cardiac arrest were randomly assigned to receive standard brain-oriented intensive care or the same standard therapy plus a single intravenous loading dose of thiopental (30 mg per kilogram of body weight). The study was designed to have an 80 percent probability of detecting a 20 percent reduction in the incidence of permanent postischemic cerebral dysfunction. Base-line characteristics were similar in the two treatment groups. At the end of one year of follow-up, there was no statistically significant difference between treatment groups in the proportion of patients who died (77 percent of the thiopental vs. 80 percent of the standard-therapy group), survived with "good" cerebral recovery (20 percent of the thiopental vs. 15 percent of the standard-therapy group), or survived with permanent severe neurologic damage (2 percent of the thiopental vs. 5 percent of the standard-therapy group). The results of this study do not support the use of thiopental for brain resuscitation after cardiac arrest.

Adolescent↗

Stability of thiopental sodium and propofol in polypropylene syringes at 23 and 4 degrees C.

The stability of thiopental sodium and propofol in an admixture stored in polypropylene syringes at room temperature and under refrigeration was studied. Propofol injection 10 mg/ mL and thiopental sodium 25 mg/mL were mixed to final concentrations of 5 and 12.5 mg/mL, respectively. The admixture was put into 60-mL polypropylene syringes, and two syringes were stored at 23 degrees C and two at 4 degrees C. For solutions stored at 23 degrees C, samples were taken at 0, 4, 8, 24, 48, 72, 120, 168, 216, 240, and 264 hours, and for samples stored at 4 degrees C, samples were taken at 0, 4, 8, 24, 48, 72, 120, 168, 216, and 312 hours. Drug concentrations were determined by high-performance liquid chromatography. Thiopental sodium and propofol retained > 90% of their initial concentrations for up to 312 hours at 4 degrees C. At 23 degrees C, > 90% of the initial concentration was retained by propofol for up to 120 hours and by thiopental sodium for up to 240 hours. No visual changes or significant change in pH occurred in any sample. When mixed and stored in polypropylene syringes, propofol 5 mg/mL and thiopental sodium 12.5 mg/mL were stable for up to 312 hours at 4 degrees C and for up to 120 hours at 23 degrees C.

Anesthetics, Intravenous↗

Thiopental and propofol impair relaxation produced by ATP-sensitive potassium channel openers in the rat aorta.

ATP-sensitive potassium channel openers are used as vasodilators in the treatment of cardiovascular disorders. The effects of i.v. anaesthetics on arterial relaxation induced by ATP-sensitive potassium channel openers have not been studied. Therefore, in this study, we have examined if thiopental (thiopentone) and propofol affect the vascular response to the ATP-sensitive potassium channel openers, cromakalim and pinacidil, in the isolated rat aorta. Rings of rat thoracic aortas without endothelium were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative manner. During submaximal contractions with phenylephrine 0.3 mumol litre-1, relaxation after cromakalim 0.1-30 mumol litre-1, pinacidil 0.1-30 mumol litre-1 and papaverine 0.1-300 mumol litre-1 was demonstrated. Thiopental 30-300 mumol litre-1, propofol 10-100 mumol litre-1, 10% Intralipid 45 microliters or glibenclamide 5 mumol litre-1 were applied 15 min before addition of phenylephrine. During contractions with phenylephrine, cromakalim and pinacidil induced concentration-dependent relaxation. A selective ATP-sensitive potassium channel antagonist, glibenclamide 5 mumol litre-1, abolished this relaxation, whereas it did not affect relaxation produced by papaverine. Thiopental concentrations > 30 mumol litre-1 significantly impaired relaxation produced by cromakalim or pinacidil. Propofol concentrations > 10 mumol litre-1 also significantly reduced relaxation produced by cromakalim or pinacidil, whereas Intralipid was ineffective. Thiopental 300 mumol litre-1 and propofol 100 mumol litre-1 did not alter relaxation produced by papaverine. These results suggest that the i.v. anaesthetics, thiopental and propofol, impaired vasodilatation mediated by ATP-sensitive potassium channels in vascular smooth muscle cells.

Adenosine Triphosphate↗