Injury due to extravasation of thiopental and propofol: Risks/effects of local cooling/warming in rats

Inadvertent leakage of medications with vesicant properties can cause severe necrosis in tissue, which can have devastating long-term consequences. The aim of this study was to evaluate the extent of extravasation injury induced by thiopental and propofol, and the effects of cooling or warming of local tissue on extravasation injury at macroscopic and histopathologic levels. Rats were administered intradermally thiopental (2.5 mg/100 µL) or propofol (1.0 mg/100 µL). Rats were assigned randomly to three groups: control (no treatment), cooling and warming. Local cooling (18–20 °C) or warming (40–42 °C) was applied for 3 h immediately after agent injection. Lesion sizes (erythema, induration, ulceration, necrosis) were monitored after agent injection. Histopathology was evaluated in skin biopsies taken 24 h after agent injection. Thiopental injection induced severe skin injury with necrosis. Peak lesions developed within 24 h and healed gradually 18–27 days after extravasation. Propofol induced inflammation but no ulceration, and lesions healed within 1–2 days. Local cooling reduced thiopental- and propofol-induced extravasation injuries but warming strongly exacerbated the skin lesions (e.g., degeneration, necrosis) induced by extravasation of thiopental and propofol. Thiopental can be classified as a “vesicant” that causes tissue necrosis and propofol can be classified as an “irritant”. Local cooling protects (at least in part) against skin disorders induced by thiopental and propofol, whereas warming is harmful.     

Membrane stabilizers inhibit potassium efflux from Staphylococcus aureus strain No. U2275

The effect of different categories of membrane stabilizers on K⁺ loss and growth has been characterized in a culture of Staphylococcus aureus. Chlorpromazine, thiopental and tetracaine at low concentrations produced a marked inhibition of K⁺ loss and an equivalent increase in the K⁺ contents of S. aureus. Whereas the inhibitory effect of chlorpromazine on K⁺ loss was observed at lower than bacteriostatic concentrations of the drug, thiopental had no effect on growth in the concentration range where K⁺ loss was maximally inhibited. It is concluded that the bacteriostatic action of chlorpromazine is probably not related to its membrane stabilizing effect only.     

Membrane composition modulates thiopental partitioning in bilayers and biomembranes

The nonspecific interaction of thiopental with erythrocyte ghosts, synaptic membranes, microsomes and mitochondria has been measured at 25°C and pH 6.6. In cholesterol-depleted erythrocyte ghosts the partition coefficient decreases with increasing cholesterol content. In sonicated liposomes made from egg lecithin and cholesterol the partition coefficient also decreases with increasing cholesterol content. The dependence of the partition coefficient on cholesterol content in the biological membranes, on average, parallels that in the lipid bilayers. The partition coefficient in lipid bilayers made from lipids extracted from erythrocyte ghosts was comparable to that in the corresponding egg lecithin/cholesterol bilayer. The partition coefficients of all the biomembranes are consistently lower than those in the corresponding egg lecithin/cholesterol bilayer, the free energy of transfer between biomembrane and corresponding bilayer being ?1 kcal/mol.     

Study of GABA<Subscript>A</Subscript> receptors on the sleep-like behavior in <Emphasis Type="Italic">Coturnix japonica</Emphasis> (Temminck Schlegel, 1849) (Galliformes: Aves)

The present study was carried out to investigate the influence of GABA_A signaling on sleep-like behaviors through systemic administration of bicuculline and picrotoxin (GABA_A antagonists) and thiopental (an allosterical modulator). A thiopental (20 mg/kg) injection increased the eye closure frequency compared to the control group. The birds quickly became sleepy with a low frequency of early behavioral stages, such as rapid oral movement (ROM), feather ruffling and blinking. A bicuculline administration (1 and 4 mg/kg) did not modify the frequency of feather ruffling, ROM, eye closure or blinking responses. A lower dose of picrotoxin (2 mg/kg) stimulated an active awakening status, while an intermediate dose (4 mg/kg) elicited a moderate awakening status, which was associated with an increase in the frequency of ROM, blinking and eye closure. At the higher dose (8 mg/kg), the birds exhibited thermoregulatory-like behaviors and convulsions immediately after the injection. Interestingly, picrotoxin (4 mg/kg) intensified the eye closures when given in combination with thiopental (20 mg/kg). Both barbiturate and picrotoxin-induced sleep-like responses have the same behavioral neuropharmacological properties, conceivably because they are correlated with action at an identical site on the GABA_A receptor.     

Differential Effects of Thiopental and Pentobarbital on Spinal GABAA Receptors

General anesthetics thiopental and pentobarbital possess very similar chemical structures whereas their clinical potency is quite different. The underlying molecular mechanism is not fully understood. This study was designed to assess the differential effects of thiopental and pentobarbital on GABA_A receptors of mechanically dissociated rat spinal dorsal horn neurons by using whole-cell patch-clamp technique. Pentobarbital, at a concentration of 30 μM, which markedly enhanced sub-saturated GABA-induced current (I _GABA), had no effect on thiopental-induced maximal current. Similarly, the pentobarbital-induced maximal current was also not affected by 30 μM thiopental. Moreover, a linear summation of thiopental-induced maximal current and pentobarbital-induced sub-maximal current was observed. In addition, pentobarbital failed to further enhance I _GABA in the presence of thiopental at a concentration with maximal modulatory effects on I _GABA, and vice versa. Our results thus suggest that thiopental and pentobarbital might exert the GABA mimetic effects independently, but share a common mechanism to produce the GABA modulatory effects. Special issue article in honor of Dr. Ji-Sheng Han.