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Biomedical subjects

L Gramstad

Publications and source records attributed to L Gramstad.

12 recordsLinked to original sources
PubMed1990

Effect of ionized calcium on the neuromuscular blocking actions of atracurium and vecuronium in the cat.

We have determined neuromuscular blocking effects of atracurium and vecuronium at normal, high and low plasma concentrations of ionized calcium ( [Ca2+] ) in the cat. Twitch responses were measured bilaterally in the anterior tibialis muscles, using intact central innervation in one preparation. Plateaus of high and low [Ca2+] were created by infusions of calcium chloride and citrate, respectively. The interactions with changes in [Ca2+] were similar for atracurium and vecuronium, and were unaffected by central muscle innervation. The median increase in [Ca2+] from 1.21 to 1.59 mmol litre-1 shifted the dose-response curves of the drugs to the right, increasing ED50 by 7-13%, whereas the decrease to median 0.78 mmol litre-1 potentiated the drugs by a similar order. This indicates a lesser influence of [Ca2+] on the action of neuromuscular blockers than reported in a previous in vitro study. Even though the interactions were statistically significant, their moderate magnitude suggests minor clinical significance.

Animals↗
PubMed1989

Midazolam does not potentiate the effect of vecuronium in patients.

Reports of midazolam interaction with vecuronium in animals prompted us to compare midazolam (0.25 mg kg-1) with thiopentone (5 mg kg-1) for possible interactions with vecuronium in patients, when used for induction of anaesthesia. After the administration of either of the two induction agents, the patients received vecuronium 0.1 mg kg-1. The onset time, duration of action and 25-75% recovery index of the neuromuscular blockade were recorded by measuring the force of thumb adduction evoked by ulnar nerve stimulation. We found no differences between patients receiving either midazolam or thiopentone in their response to vecuronium. In three of the ten patients receiving midazolam, the injection of this drug produced a 8-29% reduction of the initial twitch height.

Adult↗
PubMed1988

Comparison of large dose of vecuronium with pancuronium for prolonged neuromuscular blockade.

Dose-duration relationships for vecuronium were determined and the duration of action produced by vecuronium 0.3 mg kg-1 shown to equal that of pancuronium 0.1 mg kg-1. Using these doses, the neuromuscular blocking properties and cardiovascular effects of the two drugs were compared. With large dose administration of vecuronium (0.3 mg kg-1), both the onset time (mean 81 s) and the 25-75% recovery index (mean 13.9 min) were about one-half those associated with pancuronium (mean 168.5 s and 29.3 min, respectively). The duration of action until 25% recovery was similar with both drugs. There was no evidence of cardiovascular instability with the large dose of vecuronium. Heart rate, however, was significantly slower (range 89.7-94.2% of control) 2-20 min after the injection of vecuronium. Vecuronium 0.3 mg kg-1 may have more favourable neuromuscular blocking effects than pancuronium 0.1 mg kg-1 and may be preferable to pancuronium when prolonged neuromuscular blockade is required.

Adolescent↗
PubMed1987

Atracurium, vecuronium and pancuronium in end-stage renal failure. Dose-response properties and interactions with azathioprine.

Dose-response relations for atracurium, vecuronium and pancuronium were determined in patients in end-stage renal failure for the initial neuromuscular blockade (using three cumulative doses) and for the maintenance of stable 90% response (during continuous infusion). All measurements were during renal transplant surgery, and the interaction of azathioprine on neuromuscular blockade was estimated. Mean ED95 doses were (microgram kg-1): atracurium 375.6, vecuronium 67.2, pancuronium 86.6; the initial blockade required significantly larger doses than in normal patients (37%, 20% and 45%, respectively, using ED50 values). Mean infusion rates for 90% sustained blockade in renal failure were (microgram kg-1 h-1): atracurium 409.4, vecuronium 78.3, pancuronium 14.2. The atracurium dose was not influenced by renal function, whereas vecuronium and pancuronium requirements were significantly reduced by 23.2% and 61.5%, respectively, compared with normal patients (previous study). Azathioprine was injected at the rate of 1 mg kg-1 min-1 for 3 min at stable 90% neuromuscular blockade with constant-rate infusion of the neuromuscular blocking drug. This produced a relatively small and transient antagonism of blockade--probably of negligible clinical significance.

Adolescent↗
PubMed1986

Interaction of cyclosporin and its solvent, Cremophor, with atracurium and vecuronium. Studies in the cat.

Interactions between Sandimmun (formulated as cyclosporin (CyA) in Cremophor and ethanol) and atracurium or vecuronium were investigated in anaesthetized cats. During stable 50% blockade and with a constant rate of infusion of the neuromuscular blocking drugs, Sandimmun 0.8 mg kg-1 or an equivalent amount of its solvent moiety was injected over 5 min. Sandimmun potentiated the blockade induced by vecuronium (median infusion rate 110 micrograms kg-1 h-1) from 50.7% before injection to maximum 95.2% 17.3 min after injection (median values), whereas the median blockade in cats receiving atracurium (median 250 micrograms kg-1 h-1) increased from 51.3% to 72.4% after 32.9 min. At 45 min after the injection the median blockades were 93.1% and 69.8%, respectively. In cats receiving vecuronium (median 104 micrograms kg-1 h-1) the solvent produced an increase in effect of from 51.1% to maximum 78.0% blockade after 5.4 min and 61.5% after 45 min (median values). Interaction with solvent was negligible in cats receiving atracurium. We attribute the effect of the solvent to the Cremophor component. The mechanism of the interaction related to the cyclosporin is unknown.

Animals↗
PubMed1985

Neuromuscular blocking effects of atracurium, vecuronium and pancuronium during bolus and infusion administration.

The potencies of atracurium, vecuronium and pancuronium were compared using bolus injections and continuous infusions. The sizes of the bolus injections were based on previously determined cumulative dose-response relationships. Dose requirements for 90% and 50% sustained blockade were estimated by use of continuous infusion, and the corresponding plasma concentrations were measured for vecuronium and pancuronium. The effect of single bolus injections correlated well with the cumulative dose-responses, confirming relative potencies for atracurium, vecuronium and pancuronium of approximately 1:5:4. The maintenance doses (microgram kg-1 h-1) for 90% blockade were: atracurium 382.8, vecuronium 101.9, and pancuronium 36.9, making the relative dose requirements 10.4:2.8:1. The same dose ratio was found for atracurium and vecuronium at 50% blockade. This required about 60% of the doses needed for maintenance of 90% response. The relative potency of vecuronium and pancuronium in plasma was 1.1:1. The 25-75% recovery index was significantly shorter for vecuronium than for atracurium.

Adult↗
PubMed1982

Dose-response relation for atracurium, ORG NC 45 and pancuronium.

The potencies of atracurium, Org NC 45 and pancuronium were determined using cumulative dose-response curves. The effective doses producing 95% twitch depression were 279 microgram kg-1, 56 microgram kg-1 and 64 microgram kg-1 respectively, the relative potency being 1:5.0:4.3. The calculated log-probit dose-response curves showed the steepest slope for pancuronium, although the slopes did not deviate significantly from the parallel. The three drugs provided equal and generally good intubating conditions at approximately 95% twitch depression. Greater arterial pressure and heart rate were seen with pancuronium than with atracurium and Org NC 45.

Adult↗
PubMed1982

Onset time and duration of action for atracurium, Org NC45 and pancuronium.

Speed of onset, maximum block, duration of action and 10-25% recovery time for atracurium, Org NC 45 and pancuronium were determined using equipotent doses: 330 micrograms kg-1, 66 micrograms kg-1 and 75 micrograms kg-1 respectively. Vein-to-muscle and artery-to-muscle onset times were measured by use of simultaneous recordings. Mean speeds of onset to 95% twitch depression were: atracurium 2.7 min, Org NC 45 2.8 min and pancuronium 3.6 min. The median value of maximum neuromuscular block exceeded 98.5% for all drugs and the mean durations of action to 25% recovery of control twitch height were: atracurium 27.6 min, Org NC 45 21.9 min and pancuronium 45.1 min. The differences were statistically significant. The recovery period from 10% to 25% twitch response was considerably longer for pancuronium than for the other drugs, which did not differ significantly from each other. We were unable to validate the artery-to-muscle technique in the determination of onset time.

Adult↗
PubMed1979

Plasma viscosity and cremophor-containing anaesthetics.

The cremophor-containing anaesthetic agents, Althesin, propanidid and diazepam, were added to plasma in vitro and administered to patients. In vitro these anaesthetics, and cremophor alone in concentrations equal to those obtained in vivo, decreased the viscosity of plasma 45% at shear rate 11.5 s-1. In 11 patients given cremophor-containing anaesthetics to induce anaesthesia, plasma samples obtained 5 min after injection showed a mean decrease in viscosity of 42% compared with the pre-induction values. The effect on viscosity after a single dose disappeared in 50 min. Triton x-100 added to plasma caused a decrease in viscosity similar to that of cremophor. The interaction in vitro of cremophor and Triton x-100 with concentrated urea was found to be identical both in plasma and dextran. This suggests that cremophor acts by increasing the sheet of structured water around the protein molecules, thereby preventing the aggregation of proteins.

Adult↗