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PubMed1984

The pharmacokinetics of thiopental in pediatric surgical patients.

Thiopental pharmacokinetics and protein binding were determined in 24 pediatric surgical patients with normal hepatic and renal function, ranging in age from 5 months to 13 yr. These pharmacokinetic data were compared with those from 11 adult patients previously studied at our institution. All pediatric patients received a single intravenous bolus of thiopental, 4.0 +/- 0.08 mg . kg-1 (mean +/- SD), while the adult patients received 6.0 +/- 0.74 mg . kg-1. Distribution phase kinetics and volume of distribution at steady state (Vdss) did not differ statistically between the two groups. The degree of serum protein binding of thiopental also was similar in pediatric and adult patients with free fractions of 13.2% +/- 1.5% and 13.6% +/- 1.3%, respectively. The two patient groups showed a marked difference in elimination half-time and clearance of thiopental. Total drug clearance was 6.6 +/- 2.2 ml . kg-1 . min-1 for pediatric patients and 3.1 +/- 0.5 ml . kg-1 . min-1 for adults (P less than 0.001). The elimination half-time of 6.1 +/- 3.3 hours found in pediatric patients was significantly shorter (P less than 0.005) than that for adults, 12 +/- 6 hours. Linear regression of the pediatric data failed to achieve significance (P = 0.06) for elimination half-time to increase with age, while clearance decreased (P less than 0.001) with increasing age. The shorter elimination half-time seen in infants and children was due solely to greater hepatic clearance. Thus, recovery time after large or repeated doses may be more rapid for infants and children than for adults because of the higher clearance.

Adolescent↗
PubMed1986

Effects of chronic alcohol intake on anesthetic responses to diazepam and thiopental in rats.

The effect of chronic alcohol intake on anesthetic responses to alcohol, thiopental, or diazepam was examined in adult male Sprague-Dawley rats. Alcohol-fed animals were maintained solely on a complete balanced liquid diet containing 6.54% ethanol (w/w) for 21 days; pair-fed control animals received equal amounts of the same diet with alcohol isocalorically replaced by sucrose or dextrin. Nine hours after diets were withdrawn on the twenty-second day, the following drug/dose combinations were administered intraperitoneally to separate groups of alcohol-fed and control rats (10-15 animals in each group): ethanol 2.4, 3.2, and 4.0 g/kg; thiopental 20, 40, and 80 mg/kg; and diazepam 10, 20, and 40 mg/kg. Three different responses were assessed in every animal: 1) loss of righting reflex (induction of anesthesia); 2) response to a painful stimulus (analgesia); and 3) sleeping time (duration of anesthesia). Alcohol-fed rats compared with controls were significantly less tolerant of pain at an acute alcohol dose of 2.4 g/kg, and loss of righting reflex and sleeping time were reduced at 4.0 g/kg. All three anesthetic responses were also attenuated in alcohol-fed rats at a diazepam dose of 20 mg/kg. In contrast, none of the three responses was reduced in alcohol-fed rats at any of the three thiopental doses. Thus, chronic alcohol intake sufficient to produce tolerance to anesthetic doses of alcohol in rats also produced cross-tolerance to diazepam but not to thiopental in equianesthetic doses. These results suggest that blanket recommendations for adjusting intravenous anesthetic dosages in alcoholic humans may be inadequate as guides to anesthetic management.

Alcoholism↗
PubMed1988

Dose-related changes in the rate of cerebrospinal fluid formation and resistance to reabsorption of cerebrospinal fluid following administration of thiopental, midazolam, and etomidate in dogs.

The rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) were determined in dogs at four doses of thiopental (6, 12, 18, and 24 mg.kg-1.h-1), midazolam (0.5, 1.0, 1.5, and 2.0 mg.kg-1.h-1), and etomidate (0.86, 1.72, 2.58, and 3.44 mg.kg-1.h-1). Results were compared within and between groups and to previously reported normal values for Vf (0.030-0.054 ml/min) and Ra (220-240 cmH2O.ml-1.min) in dogs. At the two lower doses of thiopental, midazolam, or etomidate Vf was not significantly different than previously reported normal values. At the two higher doses of each drug Vf was 0.019-0.024 ml/min, significantly reduced compared to Vf at the two lower doses of each drug. The pattern of Ra data was more varied. With thiopental Ra was elevated at the lowest dose, (354 +/- 17 cmH2O.ml-1.min, mean +/- SD) reduced at the highest dose (156 +/- 19 cmH2O.ml-1.min), and not significantly different than previously reported normal values at the two intermediate doses. With midazolam Ra was elevated at the lowest and highest doses (332 +/- 25 and 378 +/- 18 cmH2O.ml-1.min) and normal at the two intermediate doses. With etomidate Ra was normal at the three lower doses and reduced at the highest dose (187 +/- 13 cmH2O.ml-1.min). It is concluded that CSF volume may be increased and the CSF pressure at which CSF volume contracts may be increased by doses of thiopental or midazolam that increase Ra, but not increased by etomidate.

Absorption↗
PubMed1989

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs: VII. Verapamil and thiopental.

To assess the role of basal anesthesia in the negative inotropic properties of verapamil, the effect of thiopental (30 mg/kg followed by 3.5 mg.kg-1.min-1) on verapamil pharmacokinetics (200 micrograms/kg iv; n = 6) and its pharmacodynamics (3 and 6 micrograms.kg-1.min-1; n = 11) in chronically instrumented dogs was studied. In the presence of thiopental, verapamil pharmacokinetics remained essentially unchanged. In contrast, anesthesia altered verapamil hemodynamic properties. In the conscious animal verapamil infusions increased heart rate (14 +/- 3 and 27 +/- 4 beats/min, respectively), cardiac output (0.22 +/- 0.07 and 0.24 +/- 0.08, l/min, respectively) and PR interval (14 +/- 2 and 25 +/- 6 ms, respectively) and slightly decreased dP/dt (-315 +/- 114 and -419 +/- 106 mmHg/s, respectively). Systemic vascular resistance (SVR) decreased at the low dose (-2.7 +/- 0.7 mmHg.1.min-1), and stroke volume decreased at the high dose (-4.4 +/- 0.6 ml). Yet the presence of thiopental resulted in an accentuation of verapamil-induced tachycardia (27 +/- 7 and 31 +/- 6 beats/min, respectively), and a decrease in stroke volume (-5.3 +/- 2.0 and -6.3 +/- 2.1 ml, respectively). At 3 micrograms.kg-1.min-1 verapamil did not increase PR interval, cardiac output, or vasodilation. Finally, at 6 micrograms.kg-1.min-1 verapamil did not decrease dP/dt and increased renal blood flow (21.8 +/- 6.4 ml/min). These data provide evidence that the negative inotropic properties of verapamil are more pronounced in the presence of thiopental. However, the role of basal anesthesia appears to be limited.

Animals↗
PubMed1990

Binding of thiopental in neonatal serum.

Protein binding of thiopental was studied in 21 samples of neonatal serum (from placental blood) and compared with protein binding in ten healthy volunteers. These infants ranged between 32 and 43 weeks of gestational age (mean, 37.7 weeks) and the adult age range was from 27 to 54 years (mean, 35.4 years). Because the unbound fraction of the drug is responsible for its pharmacologic effect, a marked difference in the protein binding between neonates and adults may be relevant to the clinician. Blood obtained from freshly delivered placentas or from adult volunteers was allowed to clot and the serum separated from the sample. A portion of the serum was sent for protein and bilirubin analysis and the remainder retained for study. This latter serum was combined with four concentrations of thiopental. These specimens were then ultrafiltered and the amount of thiopental in the ultrafiltrate (unbound) compared with the prefiltered amount (total), as measured by reverse-phase high-performance liquid chromatography. The binding studies were repeated at pH 7.2, 7.4, and 7.6 in both the adult and neonatal serum. Total protein and albumin are significantly less in neonatal serum, whereas bilirubin (total and direct) is significantly higher in neonatal serum than in adult serum (P less than 0.01). Neonatal serum was associated with significantly more unbound thiopental than adult serum at all levels of pH studied (P less than 0.005). Increasing the pH resulted in less free drug in both groups, but this reached statistical significance only in the adult group (P less than 0.025). Drug concentration had no effect on binding in the range examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Comparison of logdose and bracket protocols for determination of epinephrine arrhythmia thresholds in dogs anesthetized with thiopental-halothane.

Previous studies in dogs of anesthetic-epinephrine arrhythmias have used logdose or bracketed epinephrine infusion protocols to determine the arrhythmic dose of epinephrine (ADE) or plasma level of epinephrine at arrhythmias (PCE). Reported logdose ADE values for halothane preceded by thiopental induction (thiopental-halothane) are twice those with the bracket protocol. There are no reported PCE data for the bracket protocol, and neither protocol has been directly compared in the same dogs. Therefore, direct comparisons were made of thiopental-halothane ADE and PCE in seven dogs (group 1). Dogs were induced with thiopental (20 mg/kg), followed by halothane inhalation at end-tidal concentrations equivalent to MAC 1.25. Epinephrine infusion protocols were compared on two weekly test occasions, with the sequence and order of protocol testing randomized. Logdose ADE for four or more ventricular beats within 15 s was 3.92 +/- 0.60 micrograms/kg (mean +/- standard error), higher than the bracket ADE (2.54 +/- 0.34 micrograms/ml) (P less than 0.05). PCE at ADE were similar for both protocols, but six separate infusions of epinephrine were required to establish ADE with the logdose compared to four with the bracket protocol (P less than 0.05). These findings suggested enhanced epinephrine clearance with the logdose protocol. Therefore, five additional but similarly anesthetized dogs (group 2) were tested to determine if physiologic or hemodynamic conditions prior to epinephrine infusions ("initial conditions") were equivalent for both protocols. Protocols were modified to avoid provocation of ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of propofol and thiopental in isolated rat aorta and pulmonary artery.

This study was performed to determine if direct arterial dilating actions of propofol contribute to the drug's hypotensive actions. The effects of propofol were compared with those of thiopental on isolated vascular ring preparations from rat thoracic aorta and pulmonary artery. Thoracic aortic ring responses were evaluated in the presence and absence of endothelium, indomethacin, and N omega-nitro-L-arginine methyl ester (LNAME; a specific inhibitor of endothelium-derived relaxing factor-nitric oxide [EDRF/NO] synthase). Pulmonary artery responses were investigated with intact endothelium. After the induction of active isometric force by a predetermined EC50 dose of phenylephrine for each ring, effects of propofol (30, 100, 300 microM) and thiopental (10, 30, 100 microM) were examined. Propofol caused significant vasodilation in endothelium-intact, endothelium-denuded, and LNAME-treated aortic rings. In the endothelium-intact aortic and pulmonary artery rings, the initial vasodilation due to 30 and 100 microM propofol showed gradual and partial recovery over 15 min; 300 microM propofol caused sustained vasodilation. Endothelium-denuded rings and LNAME-pretreated endothelium-intact rings showed constant and sustained vasodilation with all propofol concentrations. Propofol also caused marked vasodilation in pulmonary arteries. In contrast, thiopental had no vasodilating effect in aortic or pulmonary artery preparations. In control experiments, propofol vehicle (Intralipid) also had no effect on vascular rings. Indomethacin pretreatment induced a dose-dependent vasoconstriction by thiopental in endothelium-intact rings and decreased the vasodilation due to propofol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of halothane, propofol, and thiopental on peripheral airway reactivity.

BACKGROUND: General anesthetics modify airway responsiveness by several mechanisms, including direct effects on airway smooth muscle and reductions in neural reflex activity. Halothane has been shown to reduce responsiveness through both of these mechanisms. The airway effects of barbiturates are controversial, and the effects of propofol are unknown. METHODS: To compare the direct effects of halothane, thiopental, and propofol in vivo, canine peripheral airways were constricted with two stimuli, histamine and hypocapnia, which are thought to directly contract smooth muscle. The authors then investigated the role of ATP-sensitive potassium (KATP) channels as a mechanism for attenuating these responses. Basenji-Greyhound (BG) dogs were anesthetized with either halothane (1.5 MAC), thiopental (7.5 mg.kg-1 x min-1 intravenously) plus fentanyl (25 micrograms intravenously every 20-30 min), or propofol (0.6 mg.kg-1 x min-1 intravenously). A wedged bronchoscope technique was used to measure peripheral airway resistance (RP). After a stable baseline was obtained, dose-response curves to histamine (50, 100, or 200 micrograms intravenous bolus) or hypocapnia (0% CO2 for 2 min with 100, 200, or 400 ml/min collateral flow) were constructed. On separate occasions, the same sublobar segments were pretreated with glibenclamide (2 mg/ml aerosol), a KATP channel blocker, and dose-response curves to hypocapnia were repeated. RESULTS: Dose-response curves to histamine were similar during all three anesthetics. Halothane decreased airway responsiveness to hypocapnia, compared with either thiopental or propofol (P < 0.05). Pretreatment with glibenclamide abolished the effect of halothane on hypocapnia-induced airway constriction. CONCLUSIONS: These results indicate that propofol afforded no benefit over thiopental or halothane in reducing peripheral airway responsiveness. Furthermore, the beneficial effects of halothane in reducing responsiveness to hypocapnia appear to be mediated by the opening of KATP channels.

Airway Resistance↗
PubMed1994

Relative potency of eltanolone, propofol, and thiopental for induction of anesthesia.

BACKGROUND: The primary purpose of this investigation was to determine the relative potency of eltanolone, a new steroid hypnotic, and propofol and thiopental when used for induction of general anesthesia. In addition, the induction characteristics of propofol and eltanolone were compared. METHODS: One hundred seventy-five patients, premedicated with lorazepam 1 mg orally, randomly received one of six different doses of either eltanolone or propofol. The probability of successful induction (defined as not responsive to verbal commands within 2 min) was related to the logarithm of the dose for each drug by means of logistic regression analysis. Estimates of ED50 and ED95 for each drug were obtained. The incidence of side effects was compared for eltanolone and propofol. The potency of thiopental was determined in a parallel study, using an identical methodology in 105 patients receiving one of seven different doses of the barbiturate. RESULTS: The relative potency of eltanolone was 3.2 times (95% confidence interval 2.7-3.8) greater than propofol and 6.0 times (5.3-6.9) greater than thiopental. ED50 and ED95 values for eltanolone were 0.46 (0.40-0.52) and 0.82 (0.68-1.28) mg.kg-1, respectively. Compared to propofol, induction of anesthesia with eltanolone is characterized by a lower incidence of injection pain (3.5% vs. 58%) and apnea (1.2% vs. 11.2%). CONCLUSIONS: Eltanolone appeared to be an effective induction agent that is 3.2 times more potent than propofol and 6 times more potent than thiopental. Its use was associated with less pain on injection than was propofol.

Adolescent↗
PubMed1996

Etomidate and thiopental inhibit the release of endothelium-derived hyperpolarizing factor in the human renal artery.

BACKGROUND: Endothelium-derived hyperpolarizing factor is thought to be a cytochrome P450-derived arachidonic acid metabolite that hyperpolarizes vascular smooth muscle cells by opening Ca(2+)-activated K+ channels (K+Ca channels). In the rabbit carotid artery both volatile and intravenous anesthetics inhibit the acetylcholine-stimulated release of endothelium-derived hyperpolarizing factor. Because the release of this factor may help to maintain vascular tone in humans under conditions of a failing nitric oxide synthesis, e.g., in atherosclerosis, the effects of two intravenous anesthetics, thiopental and etomidate, on the endothelium-derived hyperpolarizing factor-mediated relaxant response to acetylcholine were investigated in human isolated renal artery segments. METHODS: The segments were suspended in Krebs-Henseleit solution (37 degrees C) containing the cyclooxygenase inhibitor diclofenac (1 microM) and preconstricted with norepinephrine (6 microM). Relaxations caused by acetylcholine (1 microM) were compared in the presence and absence of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (0.1 mM) in control segments and in segments exposed to etomidate or thiopental (0.03-0.3 mM). In addition, the effects of the two anesthetics on the relaxant response to the nitric oxide donors glyceryl trinitrate (3 microM) and sodium nitroprusside (0.1 microM) were examined. RESULTS: The relaxant response to acetylcholine, which was resistant to both nitric oxide synthase and cyclooxygenase blockade, was markedly reduced by the K+Ca channel antagonist tetrabutyl ammonium (3 mM) and the cytochrome P450 inhibitor clotrimazole (30 microM). Both etomidate and thiopental, at a concentration of 0.3 mM, selectively attenuated the relaxant response to acetylcholine in N(G)-nitro-L-arginine-treated segments, but did not affect relaxations elicited by glyceryl trinitrate or sodium nitroprusside. CONCLUSIONS: Etomidate and thiopental inhibit the endothelium-derived hyperpolarizing factor-mediated relaxant response to acetylcholine in the human renal artery, an effect that appears to be attributable to the cytochrome P450-inhibiting properties of these anesthetics.

Anesthetics, Intravenous↗
PubMed1997

Recovery of consciousness after thiopental or propofol. Bispectral index and isolated forearm technique.

BACKGROUND: Currently, there exists no effective monitor that can predict the probability of a patient being conscious during general anesthesia. The electroencephalogram-derived bispectral index (BIS) is a promising new method to assess anesthetic adequacy. This study used the BIS to predict the probability of recovery of consciousness after a single bolus induction dose of propofol or thiopental. METHODS: Twenty unpremedicated surgical patients were anesthetized with 4 mg/kg thiopental and 20 patients with 2 mg/kg propofol. The BIS was monitored throughout the study. After induction, before administration of neuromuscular blocking agent, a tourniquet was applied to one arm and inflated above the systolic blood pressure. This allowed preservation of the ability to move the hand after neuromuscular blocking agent onset. Patients were then prompted to squeeze the investigator's hand every 30 s, until they responded to the request. At the time of response, anesthesia was reinduced and the study terminated. RESULTS: The BIS at loss of consciousness and recovery of a response was not statistically different between propofol and thiopental. No patient with a BIS less than 58 was conscious. In both groups, a BIS of less than 65 signified a less than 5% probability of return of consciousness within 50 s. CONCLUSION: The BIS can be used to predict probability of recovery of consciousness after a single injection of either thiopental or propofol.

Adult↗
PubMed2000

The effect of altered cerebral blood flow on the cerebral kinetics of thiopental and propofol in sheep.

BACKGROUND: Thiopental and propofol are highly lipid-soluble, and their entry into the brain often is assumed to be limited by cerebral blood flow rather than by a diffusion barrier. However, there is little direct experimental evidence for this assumption. METHODS: The cerebral kinetics of thiopental and propofol were examined over a range of cerebral blood flows using five and six chronically instrumented sheep, respectively. Using anesthesia (2.0% halothane), three steady state levels of cerebral blood flow (low, medium, and high) were achieved in random order by altering arterial carbon dioxide tension. For each flow state, 250 mg thiopental or 100 mg propofol was infused intravenously over 2 min. To quantify cerebral kinetics, arterial and sagittal sinus blood was sampled rapidly for 20 min from the start of the infusion, and 1.5 h was allowed between consecutive infusions. Various models of cerebral kinetics were examined for their ability to account for the data. RESULTS: The mean baseline cerebral blood flows for the "high" flow state were over threefold greater than those for the low. For the high-flow state the normalized arteriovenous concentration difference across the brain was smaller than for the low-flow state, for both drugs. The data were better described by a model with partial membrane limitation than those with only flow limitation or dispersion. CONCLUSIONS: The cerebral kinetics of thiopental and propofol after bolus injection were dependent on cerebral blood flow, despite partial diffusion limitation. Higher flows produce higher peak cerebral concentrations.

Anesthetics, Intravenous↗
PubMed2005

Propofol and thiopental do not interfere with regional cerebral blood flow response at sedative concentrations.

BACKGROUND: Anesthetics may affect the regional cerebral blood flow (rCBF) response associated with increased brain activity in humans. rCBF was measured as auditory stimulus rate was increased during propofol and thiopental administration. METHODS: After informed consent, 10 right-handed male volunteer participants (aged 33.5 +/- 10.4 yr, weighing 74.5 +/- 8.4 kg) received thiopental (n = 4) or propofol (n = 6) intravenously at stepwise target concentrations of propofol 1.2 and 2.5-3, or thiopental 4 and 7-9 microg/ml, representing sedative and hypnotic drug concentrations. The latter made volunteers unresponsive to voice or mild stimulation. Quantitative positron emission tomographic brain images were obtained at 0, 20, and 40 auditory words per minute at each drug concentration. Using SPM99 analysis, 10-mm spherical regions of interest were identified by peak covariation of word rate with rCBF across all conditions and drug concentrations. Individual mean rCBF responses in these and primary auditory cortex (Heschl's gyri) were obtained. RESULTS: Significant increases in rCBF with auditory word rate occurred in temporal lobes bilaterally at baseline (significance, T = 4.95). There was no change in this response during sedation (T = 5.60). During unresponsiveness seven of 10 participants had a diminished response in the left temporal lobe (T = 3.18). Global CBF, corrected for changes in PCO2 (3% .mmHg PCO2), was reduced 15% by sedation and 27% during unresponsiveness. CONCLUSION: The presence of propofol or thiopental does not affect the rCBF response to increasing stimulus rate during consciousness. Thus, changes in rCBF activation patterns with sedative concentrations of these drugs represent effects on brain activity itself. The neuroanatomical targets of drug effect on memory and attention may be revealed by changes in rCBF patterns associated with these cognitive activities.

Acoustic Stimulation↗
PubMed1997

Pharmacokinetics of high-dose thiopental in pediatric patients with increased intracranial pressure.

This study was conducted on 10 pediatric patients in whom intracranial hypertension stemming from head injury was reduced by high-dose thiopental administered for a prolonged period. All children showed a favorable recovery of their neurological functions. The total dose normalized to body weight averaged 335 +/- 135 mg/kg, and the mean treatment duration was 93.0 +/- 37.1 h. Data analysis was modeled for each patient to cover all the doses on the whole plasma thiopental concentration-time curve, according to a one-compartment open model. A better fit was obtained using a linear model rather than a Michaelis-Menten elimination model. Model selection was guided by evaluation of the minimum objective function, the weighted residuals, and the Akaike criterion. Thiopental pharmacokinetic parameters in pediatric patients were compared with those determined in an adult control group with similar total doses and durations of treatment. No significant difference was found between the two groups in spite of a 33% decrease of the elimination half-life in children (11.7 +/- 5.7 h) compared with adults (17.5 +/- 9.03 h). The mean values obtained were 2.42 and 2.19 ml/min/kg for total clearance and 2.18 and 2.90 L/kg for Vd in pediatric and adult groups, respectively. The linear regression of pharmacokinetic parameters in terms of age was not significant. When high doses of thiopental were administered over a prolonged period, the pharmacokinetic parameters computed for pediatric patients did not differ from those obtained in adults.

Adolescent↗
PubMed1993

Transcranial Doppler monitoring during induction of anesthesia: effects of propofol, thiopental, and hyperventilation in patients with large malignant brain tumors.

Disturbed autoregulation and CO2 reactivity have been reported in patients with brain tumors. Therefore, we decided to monitor the cerebrovascular effects of anesthetic drugs and hyperventilation. Transcranial Doppler sonography (TCD) can measure noninvasively alterations of flow velocities (v) and cross-sectional vessel area (VA) in large brain arteries. Twenty-eight patients with large malignant brain tumors in the territory of the middle cerebral artery (MCA) randomly received propofol or thiopental for induction and maintenance of anesthesia. Mean arterial pressure (MAP), heart rate (HR), and TCD parameters (vMCA and VA of the tumor or nontumor side) were determined at six data points (DP). The first measurements (MAP, HR, and TCD of the nontumor side) were performed before (DP I) and 60 s after (DP II) induction of anesthesia with either 2 mg/kg propofol or 4 mg/kg thiopental. After intubation and normoventilation (50% O2 in air), 0.05-0.1 mg/kg midazolam and an alfentanil infusion (100 micrograms/kg x h) were initiated. Then MAP, HR, vMCA, and VA of the tumor side were analyzed before (DP III) and 60 s after (DP IV) either propofol (1 mg/kg) or thiopental (2 mg/kg) were given. Finally, the effects of hyperventilation on HR, MAP, vMCA, and VA (tumor side) were determined (DP V and VI). Mean +/- SD, thiopental or propofol reactivity (non-tumor and tumor side) and CO2 reactivity (tumor side) were calculated; statistical comparison between DP I and II, III and IV, and V and VI was performed by paired t tests (p < 0.05). Unpaired t tests were used to evaluate differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Antioxidant actions and early ultrastructural findings of thiopental and propofol in experimental spinal cord injury.

Thiopental and propofol are effective antioxidant agents. The current study was undertaken to examine the neuroprotective effects of a single intraperitoneal dose of thiopental and propofol. Effects of the drugs were evaluated by lipid peroxidation and ultrastructural findings. Fifty male Wistar rats were divided into five groups. Group 1 was the control group. Rats underwent laminectomy only, and nontraumatized spinal cord samples were obtained 1 hour after surgical intervention. All other rats sustained a 50-g/cm contusion injury by the weight drop technique. Group 2 rats underwent spinal cord injury alone, group 3 rats received 1 mL intralipid solution intraperitoneally immediately after trauma as the vehicle group, group 4 rats received a 15-mg/kg single dose of thiopental, and group 5 rats received a 40-mg/kg single dose of propofol intraperitoneally following the trauma. Samples from groups 2, 3, 4, and 5 were obtained 1 hour after injury. Lipid peroxidation was determined by measuring the concentration of malondialdehyde in the spinal cord tissue. The ultrastructure of the spinal cord was determined by electron microscopy. The contusion injury was associated with a rise in lipid peroxidation. Compared with the trauma group there was significant attenuation in lipid peroxidation of groups 4 and 5. Ultrastructural findings showed that the rats of group 4 sustained minor damage after spinal cord injury, but there was more evident damage in group 5 rats. These results indicate that thiopental decreases lipid peroxidation and improves ultrastructure, whereas propofol decreases lipid peroxidation without improving ultrastructure 1 hour after spinal cord injury in rats.

Anesthetics, Intravenous↗
PubMed2004

Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia.

BACKGROUND: Time-frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. METHODS: Response entropy, SE [S/5 Entropy Module, M-ENTROPY (later in text: Entropy), Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A-2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg-1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg-1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. RESULTS: Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 +/- 22%, 75 +/- 26%, and 59 +/- 18% (mean +/- SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86+/-21%, 88 +/- 13%, and 63 +/- 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P < 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. CONCLUSIONS: All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.

Adolescent↗
PubMed1991

A comparative study of the pharmacokinetics of thiopental in the rabbit, sheep and dog.

The central arterial pharmacokinetics of thiopental were studied in six rabbits, six sheep and six dogs after a short infusion at approximately 10 mg/kg min. Thiopental was infused to a defined electro-encephalographic endpoint (EEG burst suppression). The time to reach early burst suppression was longer in the dog (3.9 +/- 0.5 min) compared with the sheep (3.0 +/- 0.6 min) and the rabbit (2.5 +/- 0.5 min). The total dose required to produce the same level of EEG activity was higher in the dog (35.9 +/- 6.8 mg/kg) compared with the sheep (24.3 +/- 5.3 mg/kg) and the rabbit (21.6 +/- 6.8 mg/kg). The plasma concentration-time data for each animal was fitted using non-linear regression to a bi- or tri-exponential function. In all animals, the plasma-time profile was best described as a tri-exponential decay. The initial volume of distribution was similar in all three species (rabbit, 38.6 +/- 10.0 mg/kg; sheep, 44.5 +/- 9.1 ml/kg; dog, 38.1 +/- 18.4 ml/kg). The maximum arterial plasma thiopental concentration achieved at EEG burst suppression was higher in the sheep (221.8 +/- 27.9 micrograms/ml) than the dog (164.7 +/- 29.9 micrograms/ml) or the rabbit (112.3 +/- 15.1 micrograms/ml). Thiopental distribution clearance was slower in the sheep (43.6 +/- 15.1 ml/min/kg) compared with the rabbit (110.5 +/- 18.7 ml/min kg) and the dog (97.2 +/- 47.2 ml/min kg). Elimination half-life was extended in the sheep (251.9 +/- 107.8 min) and dog (182.4 +/- 57.9 min) relative to the rabbit (43.1 +/- 3.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗