The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements.

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.

How does the plethysmogram derived from the pulse oximeter relate to arterial blood pressure in coronary artery bypass graft patients?

UNLABELLED: Twenty patients scheduled for coronary artery bypass grafting had their ear and finger oximeter and radial artery blood pressure (Bp(meas)) waveforms collected. The ear and finger pulse oximeter waveforms were analyzed to extract beat-to-beat amplitude and area and width measurements. The Bp(meas) waveforms were analyzed to measured systolic blood pressure (BP), mean BP, and pulse pressure. The correlation coefficient was determined between the derived waveforms from the pulse oximeter and Bp(meas) for the first 10 patients. The ear pulse oximeter width (Width(Ear)) had the best correlation (r = 0.8). Linear regression was done between Width(Ear) and Bp(meas) based on slope (b) and intercept (a) values, BP was calculated (Bp(calc)) in the next 10 patients as: [equation: see text] where i = systolic BP, mean BP, and pulse pressure. The initial bias was too large to be clinically useful. To improve clinical applicability a period of calibration was introduced in which the first 50 readings of Width(Ear) and Bp(meas) for each patient were used to calculate the intercept. After calibration the systolic BP, mean BP and pulse pressure bias values were -2.6, -1.88 and -1.28 mm Hg, and the precision values were 15.9 10.09, and 9.94 mm Hg, respectively. The present attempt to develop a clinically useful method of noninvasive BP measuring was partly successful with the requirement of a calibration period. IMPLICATIONS: Statistical comparison was made between measured blood pressure (BP) from arterial line and calculated BP derived from ear pulse oximeter waveform in 10 patients undergoing coronary artery bypass graft surgery. Using 62,077 paired readings, the mean difference for systolic BP, mean BP, and pulse pressure between the 2 methods was -2.6, -1.88, and -1.28 mm Hg, respectively.

Different responses of ear and finger pulse oximeter wave form to cold pressor test.

The cold pressor test is often used to assess vasoconstrictive responses because it simulates the vasoconstrictive challenges commonly encountered in the clinical setting. With IRB approval, 12 healthy volunteers, aged 25--50 yr, underwent baseline plethysmographic monitoring on the finger and ear. The contralateral hand was immersed in ice water for 30 s to elicit a systemic vasoconstrictive response while the recordings were continued. The changes in plethysmographic amplitude for the first 30 s of ice water immersion (period of maximum response) of the finger and ear were compared. The data indicate a significant disparity between the finger and the ear signals in response to the cold stimulus. The average finger plethysmographic amplitude measurement decreased by 48% +/- 19%. In contrast, no significant change was seen in the ear plethysmographic amplitude measurement, which decreased by 2% +/- 10%. We conclude that the ear is relatively immune to the vasoconstrictive effects. These findings suggest that the comparison of the ear and finger pulse oximeter wave forms might be used as a real-time monitor of sympathetic tone and that the ear plethysmography may be a suitable monitor of the systemic circulation.

Comparative recovery of 50-Hz and 100-Hz posttetanic twitch following profound neuromuscular block.

STUDY OBJECTIVE: To determine if posttetanic twitch following 100-Hz tetanic stimulation enables titration of a nondepolarizing relaxant infusion to a greater depth of block than that achieved with posttetanic twitch following 50 Hz. STUDY DESIGN: Prospective, observational study. SETTING: Operating rooms of a university tertiary care center. PATIENTS: 10 ASA physical status II and III patients free of known neuromuscular disease and undergoing general endotracheal anesthesia for routine elective surgery. INTERVENTIONS: Following induction of general anesthesia, neuromuscular block was maintained with a continuous intravenous vecuronium infusion. Depth of neuromuscular block was assessed by tactile evaluation of the evoked responses of the adductor pollicis muscle following supramaximal stimulation of the ulnar nerve via surface electrodes. The vecuronium infusion was titrated to loss of posttetanic twitch following 100-Hz tetanic stimulation, at which point the infusion was discontinued. MEASUREMENTS AND MAIN RESULTS: 100-Hz tetanic stimulation was repeated every two minutes until recovery of the first posttetanic twitch, at which point 50-Hz tetanic stimulation was repeated every two minutes until recovery of the first posttetanic twitch. The median time (interquartile range) from discontinuation of the vecuronium infusion to recovery of the first posttetanic twitch following 100-Hz tetanic stimulation was 27% faster than the corresponding time to recovery of the first posttetanic twitch following 50-Hz tetanic stimulation [19 (10 to 24) min and 26 (20 to 30) min respectively, p < 0.002]. CONCLUSIONS: Posttetanic twitch following 100-Hz tetanic stimulation enables titration of a vecuronium infusion to a greater depth of block than posttetanic twitch following 50-Hz tetanic stimulation. The present findings should enable more effective titration of this relaxant, thereby reducing the likelihood of unwanted patient movement or unduly prolonged recovery due to relaxant overdosing.

Efficacy and safety of divided dose administration of mivacurium for a 90-second tracheal intubation.

STUDY OBJECTIVE: To compare the safety and effectiveness of 0.25 mg divided doses of mivacurium chloride to succinylcholine for a 90-second tracheal intubation. DESIGN: Randomized, double-blind, multicenter study in two groups. SETTING: Operating rooms at four university medical centers. PATIENTS: 200 healthy ASA status I and II adult patients scheduled for elective surgery with general anesthesia and endotracheal intubation. INTERVENTIONS: Patients were premedicated with 1 to 2 mg midazolam and 2 micrograms/kg fentanyl. Anesthesia was induced with 2 mg/kg propofol. Group A received 0.25 mg/kg mivacurium given as a divided dose (0.15 mg/kg followed in 30 seconds with 0.1 mg/kg). Group B (control) received 1.5 mg/kg succinylcholine (SCh) preceded two minutes earlier by 50 micrograms/kg d-tubocurarine (dtc). MEASUREMENTS AND MAIN RESULTS: Tracheal intubation grading, train-of-four response of the adductor pollicis, heart rate (HR), and mean arterial blood pressure (MAP) were measured and evaluated. Chi-square analysis was performed for comparison between Group A and Group B with respect to the frequency distribution of intubation using the scores excellent, good, and poor and not possible (combined). Group B had a significantly higher excellent score of intubation than Group A, 84% versus 56% (p < 0.0001). No significant difference was found between the two groups when the scores excellent and good were combined (Fisher's Exact test, p = 0.28). The changes in MAP and HR were similar for the two groups. CONCLUSIONS: When Sch is not desirable, mivacurium 0.25 mg/kg given as a divided dose provides good to excellent intubation conditions 90 seconds after the initial dose without significant changes in MAP or HR. It can be an appropriate alternative for short surgical procedures. It must be emphasized that this conclusion does not apply to rapid-sequence induction-intubation.

Early neuromuscular recovery characteristics following administration of mivacurium plus vecuronium.

PURPOSE: This study was designed to describe the early recovery characteristics, as well as the speed of onset of neuromuscular block, after a combination of mivacurium and vecuronium. METHODS: In this controlled, randomized study, 30 consenting ASA I-III patients were assigned to three treatment groups. The "2M2V" group received twice the dose necessary to cause 95% depression of the evoked twitch response (2 x ED95) of mivacurium (0.15 mg.kg-1) plus 2 x ED95 of vecuronium (0.1 mg.kg-1); the "2V" group received 2 x ED95 of vecuronium; and the "4V" group received 4 x ED95 of vecuronium. Evoked neuromuscular responses of the adductor pollicis were assessed with an adductor pollicis force transducer. The time until maximum block and times to 10% and 25% recovery (T10 and T25) in each group were expressed as mean +/- standard deviation and compared using ANOVA. RESULTS: Onset of block in the 2M2V group was 27% faster than in the 2V group (2.0 +/- 0.6 vs. 2.7 +/- 0.8 min respectively, P < 0.05) and was similar to the 4V group (1.95 +/- 0.3 min, P = NS). The times until 10% recovery were similar in the 2M2V and 4V groups (59.9 +/- 12 vs 68.2 +/- 25 min, P = NS) and were slower than in the 2V groups (37.2 +/- 9 min, P < 0.05). Between T10 and T25 recovery after 2M2V resembled that after 2V (6.7 +/- 3 vs 5.7 +/- 1 min, P = NS) and was faster than after 4V (10.9 +/- 7 min, P < 0.05). CONCLUSIONS: When 2 x ED95 of mivacurium is added to 2 x ED95 of an intermediate or long-acting relaxant, recovery after T10 will proceed as if one had administered the longer-acting agent alone.

Fusicoccin Activity and Binding in Arabidopsis thaliana.

I have examined the activity and specific binding of the phytotoxin fusicoccin using Arabidopsis thaliana L. Col-O. Fusicoccin (10 micromolar) stimulates both proton extrusion and enlargement in isolated Arabidopsis leaf discs. Radiolabeled fusicoccin specifically binds to membranes (13,000 to 100,000g subcellular fraction) from cultured cells of Arabidopsis. The specific binding of this phytotoxin to putative receptor sites in Arabidopsis membranes is both pH-sensitive (pH optimum = 5.5 to 6.0) and heat-labile (10 min at 70 degrees C). The apparent dissociation constant for the specific binding at 20 degrees C is approximately 1.3 x 10(-8) molar. The results of this study are in general agreement with previous reports of fusicoccin binding and activity in other plant species.

Clinical pharmacology of mivacurium chloride (BW B1090U) infusion: comparison with vecuronium and atracurium.

Mivacurium chloride (BW B1090U) is a new, short-acting non-depolarizing neuromuscular blocking agent. It is a synthetic bis-benzylisoquinolinium diester, which is hydrolysed rapidly by plasma cholinesterase. This study compares mivacurium, atracurium and vecuronium by continuous i.v. infusion. The duration of mivacurium infusion ranged from 29.5 to 286 min. The steady state infusion rates necessary to maintain 95 (SEM 4)% twitch suppression were: mivacurium 8.3 (0.7) micrograms kg-1 min-1; atracurium 7.9 (0.4) micrograms kg-1 min-1; vecuronium 1.2 (0.3) micrograms kg-1 min-1. Following infusions of mivacurium, various recovery times (for example: 25-75%, 6.9 (0.3) min; 25-95%, 11.0 (0.4) min; 5-95% 14.5 (0.4) min) did not differ significantly from those following single bolus doses. Recovery times following cessation of mivacarium infusions were approximately 50% of those for equivalent durations of infusion of atracurium (10.9 (0.3) min for 25-75% recovery and 26.6 (0.4) min for 5-95% recovery). For vecuronium, corresponding recovery times were 13.8 (0.9) and 32.0 (1.2) min, respectively. Comparative recovery times for mivacurium were 40-50% of those for vecuronium. There was a significant correlation between the infusion rate of mivacurium required to maintain 95% twitch depression and the plasma cholinesterase activity of individual subjects.

Isoelectric focusing of oat root membranes.

The feasibility of purifying subcellular membranes, especially plasma membranes, from oat roots using isoelectric focusing has been examined. Membranes from oat (Avena sativa L. cv Garry) root homogenates were fractionated using discontinuous sucrose density gradient centrifugation and then electrofocused using a microanalytical isoelectric focusing column. The column contained either a broad-range (pH 3-10) or narrow-range (pH 3-6) pH gradient stabilized by a 5 to 15% Ficoll gradient. Results from the broad-range columns confirmed that the isoelectric pH (pI) values of the membranes were in the acidic range, with pI values ranging from 3.9 to 5.2. Using narrow-range pH gradients, it was possible to fractionate further plasma membrane-enriched material obtained from a sucrose density gradient. We had no success at fractionating crude membrane preparations from oat roots. Narrow-range pH gradients generated by commercial ampholytes were more successful than those generated by acetate/acetic acid mixtures.

Redox activity at the surface of oat root cells.

Electron transport activity at the cell surface of intact oat seedlings (Avena sativa L. cv Garry) was examined by measuring the oxidation and/or reduction of agents in the medium bathing the roots. Oxidation of NADH with or without added electron acceptors and reduction of ferricyanide by an endogenous electron donor were detected. The activities appear to be due to electron transfer at, or across, the plasma membrane and not due to reagent uptake or leakage of oxidants or reductants. NADH-ferricyanide oxidoreductase activity was also detected in plasma membrane-enriched preparations from Avena roots. Based on redox responses to pH, various ions, and to a variety of electron donors and acceptors, the results indicate that more than one electron transport system is present at the plasma membrane.

Evidence for a Cl-Stimulated MgATPase Proton Pump in Oat Root Membranes.

The possibility that plant membrane-bound MgATPases may act as electrogenic proton pumps has been investigated. Using an oat (Avena sativa L. cv. Victory) root membrane preparation which is partially enriched in tightly sealed vesicles, we have shown that MgATP stimulates the uptake of the membrane-permeable anion [(14)C]SCN(-) by the vesicles; this indicates that an electrical potential (interior positive) is generated across the membrane. Both Cl(-) ions and the proton ionophore trifluoromethoxy(carbonyl-cyanide)phenylhydrazone inhibit the MgATP-driven [(14)C]SCN(-) uptake, presumably by collapsing the MgATP-generated membrane potential. The uptake of the pH gradient probe [(14)C]imidazole into the vesicles is also greatly stimulated by MgATP, indicating the presence of a transmembrane proton gradient (interior acid). MgATP-driven [(14)C]imidazole uptake is temperature sensitive, Cl(-)-stimulated, substrate specific for MgATP, sensitive to the MgATPase inhibitors vanadate and N,N'-dicyclohexylcarbodiimide, and completely eliminated by trifluoromethoxy(carboxyl-cyanide)phenylhydrazone. The mitochondrial ATPase inhibitor oligomycin has little effect on the MgATPase activity and on the MgATP-dependent [(14)C]SCN(-) and [(14)C]imidazole uptake. These data indicate that a class of oat root membrane-bound MgATPases, stimulated primarily by Cl ions, is capable of using the free energy of ATP-hydrolysis to generate an apparent electrochemical proton gradient in vitro.

Partial characterization of fusicoccin binding to receptor sites on oat root membranes.

The possibility that fusicoccin (FC) binds to plasma membrane-associated ATPases of oat (cv. Victory) roots has been examined. Specific FC-binding in vitro is localized primarily on plasma membrane-enriched fractions. This FC-binding is greatly reduced by pretreatment of the membrane vesicles at temperatures above 45 C or with trypsin, and the same treatments cause the release of already bound FC. These results support the idea that the FC receptor is a protein located on the plasma membrane.Both active ATPases and FC-binding proteins were solubilized using 1% Triton X-100. When this material was fractionated using gel chromatography, the ATPase activity could be separated from the FC-binding proteins. The identity of the FC-binding proteins is discussed with regard to the extensive evidence which supports the involvement of plasma membrane-ATPase H(+)/K(+) pumps in FC-stimulated acidification and K(+) uptake.

The influence of the fatty acid composition of Acholeplasma laidlawii membranes on the growth inhibitory activity of narasin, a polyether ionophorous antibiotic.

Narasin, apolyether ionophorous antibiotic capable of acting as a transmembrane carrier of cations, has a growth inhibitory effect on Acholeplasma laidlawii, permitting only 20% survival when present as 0.1 micrograms/ml in an undefined growth nutrient or fatty acid-deficient nutrient supplemented only with palmitic acid. When A. laidlawii is propagated in fatty acid-deficient nutrient supplemented with linoleic acid, however, the organisms become 40 times more sensitive to the growth inhibitory effect of this antibiotic. The actual fatty acid composition of the membranes would indicate that a higher degree of unsaturation enhances ionophore activity.

Rapid auxin- and fusicoccin-enhanced Rb(+) uptake and malate synthesis in Avena coleoptile sections.

The short-term effects of auxin (indole-3-acetic acid) and fusicoccin (FC) on Rb(+) uptake and malate accumulation in Avena sativa L. coleoptile sections have been investigated. FC stimulates (86)Rb(+) uptake within 1 min while auxin-enhanced uptake begins after a 15-20-min lag period. Auxin has little or no effect on (86)Rb(+) uptake at external pHs of 6.0 or less, but substantial auxin effects can be observed in the range of pH 6.5 to 7.5. Competition studies indicate that the uptake mechanism is specific for Rb(+) and K(+). After 3 h of auxin treatment the total amount of malate in the coleoptile sections is doubled compared to control sections. FC causes a doubling of malate levels within 60 min of treatment. Auxin-induced malate accumulation exhibits a sensitivity to inhibitors and pH which is similar to that observed for the H(+)-extrusion and Rb(+)-uptake responses. Both auxin- and FC-enhanced malate accumulation are stimulated by monovalent cations but this effect is not specific for K(+).

Effects of fusicoccin on the activity of a key pH-stat enzyme, PEP-carboxylase.

The phytotoxin fusicoccin (FC) causes rapid synthesis of malate in coleoptile tissues, presumably via phosphoenolpyruvate (PEP) carboxylase coupled with malate dehydrogenase. The possibility that FC directly affects PEP carboxylase in Avena sativa L. and Zea mays L. coleoptiles was studied and rejected. The activity of this enzyme is unaffected by FC whether FC is added in vitro or a pretreatment to the live material. FC does not change the sensitivity of the enzyme to bicarbonate or malate. The activity of FC, instead, appears to be indirect. The pH sensitivity of PEP carboxylase is such that its activity, and thus the rate of malate synthesis, may be enhanced by an increase in cytoplasmic pH accompanying FC-induced H(+) excretion. Since the enzyme is also particularily sensitive to bicarbonate levels, malate synthesis may also be enhanced by FC-induced uptake or generation of CO2.