Dose-finding study of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam

Purpose We investigated the effective and safe dose of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam.Methods One hundred and eighty patients aged 20–50 years scheduled for spinal anesthesia received midazolam 0.06mg·kg^–1 and atropine 0.01mg·kg^–1 intramuscularly 15min before entering the operating room. Spinal anesthesia was performed with 0.5% hyperbaric tetracaine. Five minutes after starting surgery, midazolam 0 (control group), 0.01, 0.02, 0.03, 0.04, or 0.05mg·kg^–1 was intravenously administered (30 patients each). Blood pressure, heart rate, respiratory rate, percutaneous oxygen saturation (S_{p O 2}), verbal response, eyelash reflex, and involuntary body movement were measured every 5min for 30min. Memory during surgery was also investigated.Results The number of the patients with loss of verbal response, with loss of eyelash reflex, and with no memory during surgery were significantly larger in the groups receiving midazolam 0.03mg·kg^–1, 0.04mg·kg^–1, and 0.02mg·kg^–1, respectively. The decrease in blood pressure or increase in respiratory rate with decrease in S_{p O 2} was significantly larger in the groups receiving midazolam 0.03mg·kg^–1 or 0.05mg·kg^–1, respectively.Conclusion For sedation and amnesia of the patients aged 20–50 years in spinal anesthesia with about 1h duration receiving intramuscular midazolam 0.06mg·kg^–1 as a premedication, intravenous midazolam 0.02mg·kg^–1 might be effective and safe.     

Addition of epinephrine to intrathecal tetracaine augments depression of the bispectral index during intraoperative propofol sedation

Purpose Epinephrine added to local anesthetic agents for spinal anesthesia is frequently used to prolong the duration of anesthesia. Epinephrine stimulates the -adrenoceptor, and it is known that the 2-adrenoceptor agonists have a central inhibitory effect. We investigated the effect of intrathecal epinephrine during propofol sedation with spinal anesthesia, using a bispectral index (BIS) monitor.Methods Twenty adult patients, scheduled for spinal anesthesia, were allocated to the control group (n = 10) or epinephrine group (n = 10). Patients in the control group received 14mg of tetracaine, whereas the epinephrine group received 14mg of tetracaine and 0.2mg of epinephrine. Immediately after the pinprick test, propofol was administered at 0.5mg·kg^–1 by infusion for the initial dose, then continuously at 2mg·kg^–1·h^–1 in both groups. BIS scores were recorded before subarachnoid block, and then every 5min for 90min after subarachnoid block.Results There were significant differences in the BIS score between the two groups at 45–55min and at 60–70min after subarachnoid block.Conclusion Intrathecal epinephrine augments the sedative effect of propofol during spinal anesthesia.     

The cardiovascular effects of atracurium and it's metabolite

The administration of atracurium to humans has been reported to produce little cardiovascular effects in clinical doses. The cardiovascular effect, histamine-releasing and catecholamine releasing effects of intravenous injection of atracurium 0.6 and 1.2mg·kg^–1 were studied in man, and also the cardiovascular and catecholamine releasing effects of laudanosine which is a metabolite of atracurium by Hofmann degeneration, were studied in dogs. The increase in human plasma concentration of histamine, hypotension and tachycardia were found with the dose of atracurium 1.2mg·kg^–1. The intravenous administration of laudanosine 10µg·kg^–1 to dogs produced minimal epinephrine, norepinephrine releases and cardiovascular changes.(Fukushima K, Aoki T, Watanabe K et al.: The cardiovascular effects of atracurium and its metabolite. J Anesth 4: 45–50, 1990)     

Comparison of adjuvant anesthetics for propofol induction

Purpose.Fentanyl was compared with nitrous oxide/sevoflurane as an adjuvant anesthesia to propofol during induction.Methods.Two-hundred sixty-three patients of American Society of Anesthesiologists physical status 1 or 2 undergoing minor surgery were randomly divided into two groups. Group F patients (n = 125) received 2g·kg^–1 fentanyl and 1.8mg·kg^–1 propofol, and were ventilated by mask with oxygen. Group S patients (n = 138) received 1.8mg·kg^–1 propofol, followed by inhalation of 4% sevoflurane in N₂O (4l·min^–1) and oxygen (2l·min^–1) by mask. The trachea was intubated exactly 2, 3, 4, or 5min after injection of 0.1mg·kg^–1 vecuronium, and the conditions of endotracheal intubation were scored according to the patients' responses to laryngoscopy and endotracheal intubation. Systolic blood pressure (SBP) and heart rate (HR) were measured before and after endotracheal intubation. The cost of anesthetics was also calculated.Results.No significant differences in SBP were observed between the groups throughout the induction period. HR did not change from preanesthetic values in group F. In contrast, HR in group S patients increased by 9–18 beats·min^–1 (bpm) after inhalation of N₂O/sevoflurane and further increased by 17–21bpm following endotracheal intubation. Significant differences in HR were noticed between the groups (P 0.001). The conditions of endotracheal intubation were similar in the two groups and were satisfactory when mask ventilation exceeded 3min. Fentanyl was less expensive than sevoflurane/N₂O anesthesia when mask ventilation exceeded 3min.Conclusion.From the standpoints of hemodynamics and drug cost, fentanyl is preferable to N₂O/sevoflurane inhalation as an adjuvant to propofol during induction, because mask ventilation for more than 3min was required for satisfactory endotracheal intubation.     

Plasma concentration for optimal sedation and total body clearance of propofol in patients after esophagectomy

The present study investigated plasma propofol concentration for optimal sedation and total body clearance in patients who required sedation for mechanical ventilation after esophagectomy. Seven patients after esophagectomy were enrolled in this study. Plasma propofol concentrations were measured with high performance liquid chromatography. Total body clearance was calculated from the steady-state concentration. The infusion rate of propofol for achieving the sedation score of level 3 (drowsy, responds to verbal stimulation) was 1.74 ± 0.82mgkg^–1h^–1 (mean ± SD, n = 7) when the plasma propofol concentration and the total body clearance were 0.85 ± 0.24µgml^–1 and 1.83 ± 0.54lmin^–1 (mean ± SD, n =7), respectively.     

Propofol inhibits lidocaine metabolism in human and rat liver microsomes

Purpose.When two drugs are metabolized by similar P450 isoforms, one drug inhibits the metabolism of the other when both the present. The metabolism of lidocaine and propofol can be mediated by similar P450 isoforms. Therefore, we investigated the relationship in the metabolism between lidocaine and propofol in both rat and human liver microsomal P450 (CYP) systems in vitro. Methods.(1) Propofol, 4µg·ml^–1, as the substrate and lidocaine (between 0.5 and 8µg·ml^–1) and (2) lidocaine, 4.7µg·ml^–1, as the substrate and propofol (between 0.5 and 40µg·ml^–1) were reacted separately with human and rat microsomes. The concentrations of lidocaine, its major metabolite (monoethylglycinexylidide, MEGX) and propofol were measured using high-pressure liquid chromatography. The metabolism of lidocaine was presented as a reaction activity (MEGX/lidocaine). Results.The dose-dependent inhibitory effects of propofol on lidocaine metabolism were observed in both the human and rat groups. The IC50 (the concentration producing 50% maximal inhibition) of propofol was 5.0µg·ml^–1 and 0.70µg·ml^–1 in the human and the rat groups, respectively. The propofol concentration of 5.0µg·ml^–1 is within the range of clinical doses for humans. On the other hand, lidocaine did not change propofol metabolism. Conclusion.Propofol possesses a dose-dependent inhibitory effect on the metabolism of lidocaine in both human and rat CYP systems in vitro.     

Changes in the plasma histamine concentration after the administration of vecuronium bromide

Clinical symptoms of anaphylactoid reaction to muscle relaxants vary from localized flush to cardiovascular collapse. Vecuronium bromide is reported to have very little histamine releasing property. However, there are some reports of anaphylaxis or anaphylactoid reaction to vecuronium. We studied plasma histamine concentration after the intravenous injection of vecuronium to confirm the histamine release. Twenty patients were randomly allocated to one of two groups, each group comprising of 10 patients: one group was to receive vecuronium 0.1mg·kg^–1 and the other 0.2mg·kg^–1 using the priming principle. Blood samples were taken prior to and 1, 3, 5, 8 and 13min after the administration of vecuronium. The plasma histamine concentration was measured by radioimmunoassay with monoclonal antibody.There were no significant changes in plasma histamine concentration over 13min after the administration of vecuronium compared with the baseline value. There were also no significant differences between these two groups. We concluded that vecuronium up to 0.2mg·kg^–1 did not change the plasma histamine concentration in the patients having no previous history of allergy or atopic tendencies.(Mitsuhata H, Matsumoto S, Enzan K, et al.: Changes in the plasma histamine concentration after the administration of vecronium bromide. J Anesth 5: 24–29, 1991)     

Cyclic alteration in the anticonvulsant effect of nitrous oxide in rats

The anticonvulsant action of nitrous oxide and its time course were studied in rats. Bicuculline, a GABA-receptor antagonist, was administered intravenously at a rate of 0.2mg·kg^–1·min^–1 during exposure to air (n = 60) or 75% nitrous oxide in oxygen (n = 80). The convulsant dose of bicuculline was determined. The rats were divided into subgroups according to the duration of exposure to air or nitrous oxide, from 0 to 120min at 15min intervals. Although the convulsant dose of bicuculline was consistent in the air group (1.03 ± 0.06mg·kg^–1, mean ± SEM), it showed two peaks at 30- and 90min exposures to nitrous oxide. The threshold dose in the nitrous oxide group was significantly higher than in the air group at only 15- and 30min exposures (1.50 ± 0.16, 2.15 ± 0.25mg·kg^–1, respectively, P 0.05). We conclude that nitrous oxide has an anticonvulsant action against bicuculline-induced seizure, and that a cyclic nature exists in its action.(Shingu K, Osawa M, Mori K: Cyclic alteration in the anticonvulsant effect of nitrous oxide in rats. J Anesth 4: 309–312, 1990)     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

The N-Methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enfturane-induced opisthotonus in mice

We determined whether enflurane-induced opisthotonus in ddN mice is mediated by N-methyl-D-aspartate (NMDA) receptor using NMDA receptor antagonists dizocilpine (MK-801) and ketamine. Animals were given intraperitoneal injections of 0.2ml saline (control), 2.5 or 5.0mg·kg^–1 dizocilpine in saline, or 20 or 40mg·kg^–1 ketamine is saline 20min prior to exposure to 2.0% enflurane. Incidence of opisthotonus measured during exposure to enflurane for 20min was 49% (n = 51) in saline (control) group, 6.7 (P 0.01 vs control, n = 30) and 15.0% (P 0.01, n = 40) in 2.5 and 5.0mg·kg^–1 dizocilpine group, respectively, and 43.9 (NS, n = 41) and 40.0% (NS, n = 40) in 20 and 40mg·kg^–1 ketamine group, respectively. These results strongly suggest that enflurane-induced opisthotonus is mediated by NMDA receptor. Ketamine failed to suppress significantly due to possibly small dosages. Further, dizocilpine itself produced severe seizures during preenflurane period (30.0 and 40.0% in 2.5 and 5.0mg·kg^–1, respectively), which may be a novel finding.(Komatsu H, Nogaya J, Anabuki D, et al.: The N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enflurane-induced opisthotonus in mice. J Anesth 7: 519–522, 1993)     

The relaxing effects of barbiturates in vascular smooth muscle of rat aorta

The effects of thiamylal and pentobarbital on contractions mediated through the influx of extracellular Ca⁺⁺ and the release of intracellularly stored Ca⁺⁺ were compared in rat aortic strips. Thiamylal (3 × 10^–5M to 10^–3M) and pentobarbital (10^–4 to 10^–3M) significantly attenuated the contraction induced by KCl (20mM), and shifted the dose-response curve for Ca⁺⁺ of KCl (20mM)-treated strips downwards and to the right. Caffeine (10^–2M)-induced contraction was significantly attenuated by thiamylal at concentrations greater than 10^–4M and by pentobarbital at 3 × 10^–4M. Only a high concentration (10^–3M) of these barbiturates significantly inhibited the contractions induced by norepinephrine (NE, 10^–6M) in Ca⁺⁺-free medium. Contraction of strips without endothelium by a Ca⁺⁺ ionophore, A23187 (5 × 10^–6M), in the presence of a Ca channel blocker, was relaxed by high concentrations of thiamylal (3 × 10^–4M to 10^–3M) and pentobarbital (10^–3M). It is concluded that thiamylal inhibits contraction through an intracellular action as well as a Ca channel-blocking action in vascular smooth muscle of rat aorta. However, the intracellular action of pentobarbital is less potent than that of thiamylal.(Nishiwada M, Nakamura K, Hatano Y, et al.: The relaxing effects of barbiturates in vascular smooth muscle of rat aorta. J Anesth 5: 380–387, 1991)     

Dose effects of propofol on hemodynamic and cytokine responses to endotoxemia in rats

Purpose Our previous studies have demonstrated that propofol inhibits hypotension, metabolic acidosis, and cytokine responses and reduces mortality in endotoxemic rats. The purpose of this study was to elucidate whether these beneficial effects of propofol on hemodynamics and cytokine responses were dose related.Methods Forty-eight rats were divided at random among four equal groups: groups S, M, and L received intravenous propofol administration (5, 10, and 20mg·kg^–1·h^–1, respectively) immediately after endotoxin (Escherichia coli endotoxin; 15mg·kg^–1, i.v.) was given. Group E received endotoxin alone. We assessed hemodynamics and plasma cytokine [tumor necrosis factor (TNF)- and interleukin (IL)-6] concentrations for 5h following endotoxin injection.Results Systolic arterial pressure (SAP) was significantly higher at 4 and 5h in groups S and M than in group E (P < 0.05), although SAP decreased progressively in all groups. Endotoxin injection increased the TNF- and IL-6 concentrations in all groups. The increase in TNF- concentrations at 2h was significantly lower in group M than in group E (P < 0.05). On the other hand, the increase in IL-6 concentration at 5h was significantly lower in groups M and L than in group E (P < 0.05).Conclusion The effects of propofol on blood pressure and cytokine responses were influenced by the dose of propofol, although the relationship did not follow simple linearity.     

The effects of sevoflurane on lidocaine-induced convulsions

The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean ± SD) was 41.4 ± 6.5mg·l ^–1 with lidocaine infusion (6mg·kg^–1·min^–1), increasing significantly to 66.6 ± 10.9mg·l ^–1 when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 ± 8.7mg·l ^–1) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10ng) had a tendency to decrease the convulsive threshold (21.6 ± 2.2 to 19.9 ± 2.5mg·l ^–1) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.(Karasawa F: The effects of sevoflurane on lidocaine-induced convulsions. J Anesth 5: 60–67, 1991)     

Bench test assessment of the new Raumedic Neurovent-P ICP sensor: a technical report by the BrainIT group

Summary. Background. In clinical practice, fiberberoptic and piezo-electric ICP probes are often used for measuring intracranial pressure (ICP). A number of similar technologies, although performing well in bench test studies, have been shown to exhibit unacceptable zero drift, fragility or both during trials conducted under clinical conditions. Recently, a new technology has become available, the Neurovent-P (Raumedic AG+CO, Raumedic, Germany). As a pre-requisite for a clinical trial, we have conducted and report on bench test studies to confirm the manufacturers long term zero-drift performance for this technology.Method. In a test rig static tests (recording of 20mmHg pressure) and dynamic tests, ranging from 5 to 50mmHg have been performed.Findings. 10 ICP probes have been tested for a total of 60 days. All the catheters, after the connection with the ICU monitor displayed a static pressure of 0±1mmHg and did not required pre-insertion alteration. At five days, mean zero drift was 0.6±0.9mmHg. Overall, zero drift ranged from 0 to 2mmHg. At a fixed static pressure of 20mmHg, the mean recorded value was 20.6±0.8mmHg, ranging from 19 to 23mmHg. A regression analysis of the relationship between the applied pressure and the recorded pressure during the dynamic tests of the 10 catheters yielded a correlation coefficient R² of 0.997. Applying the Altman and Bland method to assess the bias and confidence limits for the Raumedic catheter responses during the dynamic tests against the applied gold-standard hydrostatic column pressures, the average bias of –0.66±0.85mmHg, with 95% CLs of –2mmHg and 1mmHg.Conclusions. Mean zero drift, after five days, was very small and long-term continuous recording of a stable pressure was very precise. The response at dynamic tests, i.e. the changes of pressure in a wide range, was excellent. The average bias of the Raumedic catheter compared with the hydrostatic column is very small. After this bench test, the next and most critical step will be to conduct a trial of this promising technology under more demanding clinical environment.     

Elevation of the extracellular glutamate concentration in the hippocampus after total cerebral ischemia related to the deterioration of the recovery in EEG and evoked potentials in dogs

The concentrations of extracellular glutamate (Glu), aspartate (Asp) and glycine (Gly) were measured by microdialysis method in the cortex and hippocampus before, during and after 15min of total cerebral ischemia in dogs. The correlations between the concentrations of amino acids and the changes in EEG and evoked potentials (EP) after ischemia were evaluated. Total cerebral ischemia was achieved by occluding the ascending aorta and the caval veins. The concentrations of Glu in the hippocampus significantly increased from 1.73 ± 0.59 (mean ± SEM) nmol·ml^–1 at pre-ischemia to 5.46 ± 1.34 (P 0.05) during ischemia and 14.37 ± 3.70 (P 0.01) 0–15min after ischemia, and returned to the pre-ischemic level 30min after ischemia. The concentration of hippocampal Glu 0–15min after ischemia had significant negative correlations with the EEG-EP scores (0 = serious deterioration of electrical function and 6 = normal electrical function) 30min, 3hr and 5hr after ischemia (r = –0.69, P 0.05:r = –0.67, P 0.05:r = –0.70, P 0.05, respectively). The increase of the extracellular Glu concentration in the hippocampus immediately after ischemia may aggravate the neurological outcome after total cerebral ischemia.(Ono K, Iwatsuki N, Tajima T, et al.: Elevation of the extracellular glutamate concentration in the hippocampus after total cerebral ischemia related to the deterioration of the recovery in EEG and evoked potentials in dogs. J Anesth 7: 334–340, 1993)     

Respiration by tracheal insufflation of oxygen (TRIO) at high flow rates in apneic dogs

Tracheal insufflation of oxygen (TRIO) is a technique in which oxygen is introduced into the trachea at a constant flow rate via a catheter advanced to the level of the carina. We studied the effects of flow rates (0.5, 1.0, 1.5 and 2.0l·kg^–1·min^–1) on arterial blood gases during TRIO in 6 apneic dogs. The constant flow was administered through the tip of a catheter (I.D. 2.0mm) advanced to a site of 1cm above the carina. After 30min of TRIO, the mean Pa_{CO 2} at the flow rates of 0.5, 1.0, 1.5 and 2.0l·kg^–1·min^–1 were 88 ± 20, 76 ± 20, 64 ± 23 and 52 ± 18mmHg, respectively. CO₂ elimination increased as the flow rates increased from 0.5 to 2.0l·kg^–1·min^–1.Based on the above study, we examined the effects of TRIO at a flow rate of 3l·kg^–1·min^–1 in another 5 apneic dogs. TRIO, at a flow rate of 3l·kg^–1·min^–1, was able to maintain normocarbia over 4hr. The mean Pa_{O 2} and Pa_{CO 2} at 4.0hr were 465 ± 77 and 41 ± 4mmHg. Although the mechanism of pulmonary gas exchange during TRIO is unclear, our study is the first to document that normocarbia can be maintained by high-flow TRIO in apneic dots.(Urata K, Okamoto K and Morioka T.: Respiration by tracheal insufflation of oxygen (TRIO) at high flow rates in apneic dogs. J Anesth 5: 153–159, 1991)     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Recombinant human-type SOD attenuates circulatory disorders after reperfusion of splanchnic organs in rats

Oxygen free radicals (OFRs) have been reported to play pivotal roles in the pathogenesis of cell damage induced by ischemia and reperfusion. The efficacy of recombinant human superoxide dismutase (rh-SOD) in the treatment of circulatory disorders after reperfusion of the splanchnic area was investigated in rats. All rats died within 3 hours after release of 60-min superior mesenteric artery occlusion (SMAO) when no treatment was given. Animals which received rh-SOD, 2mg·100g^–1BW, at reperfusion followed by a continuous infusion of rh-SOD 0.67mg·100g^–1BW·hr^–1, exhibited prolonged survival times compared with no treatment rats (231 ± 35min and 149 ± 43min, respectively). Mean blood pressure in rats treated with rh-SOD was higher than in controls after reperfusion, and was concomitant with improvement in splanchnic perfusion. The results suggest excessive activity of OFRs in reperfused organs and a possible scavenging effect of rh-SOD as a means of eliminating them.(Bitoh H: Recombinant human-type SOD attenuates circulatory disorders after reperfusion of splanchnic organs in rats. J Anesth 6: 247–254, 1992)     

Difference in the effect of pancuronium and vecuronium on baroreflex control of heart rate in humans

The effects of pancuronium and vecuronium, each in doses of 0.05 and 0.08mg·kg^–1, on the baroreflex control of the heart rate were studied in 40 adult patients of either sex (21 men and 19 women) during stable nitrous oxide-oxygen-fentanyl anesthesia. The blood pressure was elevated by intravenous infusion of phenylephrine (4µg·kg^–1·min^–1) for the pressor test, and lowered by a bolus injection of nitroglycerin (0.3–0.5mg) for the depressor test. Baroreflex sensitivity was judged from the slope of the regression of the systolic blood pressure on the succeeding R-R intervals on the ECG. There was no significant difference between the baseline blood pressure at which both tests were carried out. Nitrous oxide-oxygen-fentanyl anesthesia alone suppressed the baroreflex sensitivity to a level which was at the lower limit of the physiological and non-anesthetized state. The 0.08mg·kg^–1 dose of pancuronium significantly suppressed the reflex sensitivity in both the pressor and depressor tests. However, the 0.05mg·kg^–1 dose of pancuronium and both doses of vecuronium did not cause any significant change in the test results.(Tsuchida H, Seki S, Nakae Y, et al.: Difference in the effect of pancuronium and vecuronium on baroreflex control of heart rate in humans. J Anesth 5: 255–259, 1991)