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UNLABELLED The efficacy of epinephrine in prolonging spinal analgesia has recently been confirmed in the lumbosacral but not in the thoracic, segments. Most previous studies used doses of epinephrine smaller than 0.3 mg. We studied the effects of 0.2, 0.4, or 0.6 mg of epinephrine added to hyperbaric lidocaine 60 mg in 7.5% dextrose solution for spinal anesthesia. Eighty patients were randomly divided into four groups: Group A received lidocaine without epinephrine, Group B received lidocaine plus 0.2 mL (0.2 mg) of epinephrine 1:1000 solution, Group C received lidocaine plus 0.4 mL (0.4 mg) of epinephrine, and Group D received lidocaine plus 0.6 mL (0.6 mg) of epinephrine. The maximal cephalad sensory level was between T2 and T3 for all groups. The median times for analgesia to regress two and four segments were significantly prolonged in Group D, but not in either Group B or C, compared with those in Group A. Times for regression to T12 and L3 were significantly prolonged in Groups B, C, and D compared with Group A. We conclude that the dose-dependent relationship of spinal analgesia can be applied to epinephrine, and that larger doses prolong lidocaine spinal anesthesia in the thoracic as well as the lumbosacral dermatomes. IMPLICATIONS Prolongation of lidocaine spinal analgesia by intrathecal epinephrine is established in the lumbosacral, but not in the thoracic, dermatomes. Three doses of epinephrine--0.2, 0.4, and 0.6 mg--were compared. A dose-dependent response and significant prolongation with the 0.6-mg dose in the thoracic dermatomes were confirmed.

Previous studies have failed to demonstrate a block of the endocrine response to upper abdominal surgery by thoracic epidural analgesia. To clarify the bases for this failure, we compared the effects of epidural analgesia of different dermatome levels up to C8-T2 or C3-4. The patients who received general anesthesia alone showed significant increases of adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) immediately after skin incision. The patients with C8-T2 blocked developed significant increases in these hormones, not after the skin incision, but after the intraabdominal procedure. Of the eight patients with C3-4 block, six developed no such responses throughout the study period. The responses of oxytocin (OXT) and prolactin (PRL) were more susceptible to epidural analgesia and were blocked at the C8-T2 level. Growth hormone (GH) showed no correlation with surgical procedures and epidural block. These findings indicate that the nociceptive neural information during upper abdominal surgery is conveyed by the sensory fibers included in both the thoracic and lumbar spinal nerves that innervate the abdominal wall and the intraabdominal viscera, and by the phrenic nerves that innervate the diaphragm. The rationale for postulating the involvement of the phrenic nerves can be referred to the embryonal descent of the diaphragm from the C3-5 myotomes that serves as the upper wall of the abdominal cavity.

Since volatile anesthetics, barbiturates, and local anesthetics have been reported to inhibit endothelium-dependent relaxation, we hypothesized that any drug with anesthetic action would suppress this relaxation. In the present study, using rat thoracic aortae, we attempted to determine whether nonbarbiturate intravenous anesthetics, including midazolam, propofol, and ketamine, suppress endothelium-dependent relaxation, and to clarify the mechanism(s) involved. Acetylcholine-induced, endothelium-dependent relaxation was significantly attenuated by propofol and ketamine, but was unaffected by midazolam. Sodium nitroprusside (SNP)-induced relaxation was attenuated by propofol, but not by midazolam or ketamine. The acetylcholine-stimulated 3',5'-cyclic guanosine monophosphate (cGMP) level was reduced by pretreatment with propofol and ketamine but not by midazolam, and that stimulated by SNP was reduced by propofol but not by ketamine or midazolam. We conclude that propofol and ketamine suppress endothelium-dependent relaxation, whereas midazolam has no influence. Moreover, the suppressive effect of ketamine on endothelium-dependent relaxation is mediated by suppression of nitrous oxide (NO) formation, whereas that of propofol may be mediated at least partly by suppression of NO function.

General anesthetics, including halothane, isoflurane, and barbiturates, suppress endothelium-dependent formation of 3',5'-cyclic guanosine monophosphate (cGMP) in the systemic and cerebral vasculature. The present study was conducted to determine whether these anesthetics have similar effects on the nitric oxide (NO)-cGMP system in the brain, and to elucidate the mechanism responsible. In rat cerebellar slices, formation of cGMP was suppressed by halothane after stimulation by N-methyl-D-aspartate (NMDA, 0.1 mM) and D-aspartate (1.0 mM) but not after stimulation by sodium nitroprusside (SNP, 0.3 mM). Isoflurane (2%) suppressed NMDA (0.1 mM)-stimulated, but not D-aspartate (1.0 mM)- and nitroprusside (0.3 mM)-stimulated formation of cGMP. In contrast, thiopental (0.1-1.0 mM) suppressed NMDA (0.1 mM)-, D-aspartate (1.0 mM)-, and nitroprusside (0.3 mM)-stimulated formation of cGMP. Treatment with aminophylline (0.1 mM), a phosphodiesterase inhibitor, did not influence the effect of thiopental, suggesting that the effect of thiopental was not mediated by activation of phosphodiesterase. D-Aspartate increases intracellular calcium, which in turn activates NO synthase, and nitroprusside generates NO without activation of NO synthase. Therefore, the present findings strongly suggest that halothane inactivates NO synthase (or related cofactors) without marked interaction with the NMDA receptor, that isoflurane may interact with the NMDA receptor, receptor-coupled G-protein, or calcium channels, and that thiopental suppresses guanylate cyclase activity.

The inhibitory effects of volatile and local, but not intravenous, anesthetics on endothelium-dependent relaxations of blood vessels have been demonstrated in vitro by several investigators. The aim of this study was to determine the effects of barbiturates on endothelium-dependent arterial relaxation and elucidate the mechanism(s) responsible. Canine mesenteric arteries and rat aortae were isolated, and tension changes in helical strips were recorded. Endothelium-dependent relaxations elicited by acetylcholine and bradykinin in canine mesenteric arteries, and those by acetylcholine in rat aortae, were significantly attenuated by thiopental (3 x 10(-4) M) pretreatment. Sodium nitroprusside (SNP)-induced, endothelium-independent relaxations were significantly attenuated by thiopental (10(-4)-3 x 10(-4) M). The effects of pentobarbital were less marked than those of thiopental. Acetylcholine (10(-5) M)-stimulated levels of 3',5'-cyclic guanosine monophosphate (cGMP) in rat aortae were reduced significantly by thiopental and pentobarbital (both 10(-3) M), and SNP (3 x 10(-7) M)-stimulated levels were reduced by thiopental (3 x 10(-4)-10(-3) M) and pentobarbital (10(-3) M). We conclude that barbiturates inhibit cGMP-mediated endothelium-dependent and independent arterial relaxations. Inhibition of endothelium-dependent relaxation by barbiturates may be mediated by their effects on vascular smooth muscle itself and not on endothelium.

Hepatic blood flow (HBF) and energy metabolism during moderate hypotension induced by prostaglandin E1 (PGE1) and nicardipine were studied by in vivo magnetic resonance spectroscopy. HBF was determined by the deuterated water clearance method by using deuterium magnetic resonance spectroscopy, and energy metabolism was estimated from the changes in the levels of adenosine triphosphate and inorganic phosphate by using phosphorus (31P) magnetic resonance spectroscopy. Mean arterial blood pressure was intentionally reduced to 60% of control with PGE1 (n = 5) or nicardipine (n = 5). The HBF decreased by 38% and by 50% during the hypotension induced by PGE1 and nicardipine, respectively. The level of adenosine triphosphate decreased by 12% and that of inorganic phosphate increased by 80% during nicardipine-induced hypotension, whereas the corresponding levels showed no remarkable changes during PGE1-induced hypotension. After the cessation of drug administration, mean arterial blood pressure and HBF recovered to the control levels in the PGE1 group, but not completely in the nicardipine group. In the latter group, the level of inorganic phosphate did not recover either. These results indicate that during hypotension induced with PGE1 hepatic circulation and metabolism are conserved to a greater extent than during hypotension induced with nicardipine.

In the course of celiac plexus alcohol block, facial flushing, palpitations, and hypotension are occasionally incurred in some patients. We hypothesized that the phenomenon represents acetaldehyde syndrome, not response to increased blood levels of ethanol as might be supposed. In order to prove our hypothesis, we selected five patients scheduled to undergo celiac plexus alcohol block, and, with their consent, we measured blood concentration of ethanol and acetaldehyde before and for 6 hr after the block. We also determined the phenotypes of aldehyde dehydrogenase (ALDH) in their hair roots. We found that "flushers" are found exclusively among subjects without ALDH I, and that their blood levels of acetaldehyde were significantly higher than those of "non-flushers" within 10 min after the block. The flushers also gave histories of facial flushing after ingestion of small amounts of ethanol. On the basis of such histories one can anticipate whether acetaldehyde syndrome is likely or unlikely to accompany the block.