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Biomedical subjects

F Donati

Publications and source records attributed to F Donati.

At least 145 records · Page 8Linked to original sources
PubMed1990

Influence of extreme obesity on the body disposition and neuromuscular blocking effect of atracurium.

The pharmacokinetics and pharmacodynamics of atracurium, a nondepolarizing neuromuscular blocking agent, were compared between morbidly obese patients and nonobese patients. Atracurium besylate (0.2 mg/kg) was administered intravenously as a bolus to patients who had received anesthesia. The force of contraction of the adductor pollicis was measured and plasma samples were collected for a 2-hour period. The concentrations of atracurium and its major end product, laudanosine, were determined by use of a chromatographic method. The pharmacokinetic-pharmacodynamic relationship was characterized by use of several models. No difference was observed between obese patients and nonobese patients in atracurium elimination half-life (19.8 +/- 0.7 versus 19.7 +/- 0.7 minutes), volume of distribution at steady state (8.6 +/- 0.7 versus 8.5 +/- 0.7 L), and total clearance (444 +/- 29 versus 404 +/- 25 ml/min). However, if values were expressed on a total body weight basis, there was a difference between obese and nonobese patients in the volume of distribution at steady state (0.067 versus 0.141 L/kg) and total clearance (3.5 +/- 0.2 versus 6.6 +/- 0.5 ml/min/kg). Although atracurium concentrations were consistently higher in obese patients than in nonobese patients, there was no difference in the time of recovery from neuromuscular blockade between the two groups. Consequently, the median effective concentration was higher in obese than in nonobese patients (470 +/- 46 versus 312 +/- 33 ng/ml).

Adult↗
PubMed1990

Edrophonium antagonism of atracurium during enflurane anaesthesia.

To determine the influence of enflurane on the ability of edrophonium to antagonize atracurium block, dose-response curves were constructed for edrophonium in the presence of 0%, 1% and 2% enflurane, and for 2% enflurane discontinued at the time of administration of edrophonium. One hundred ASA Physical Status I or II patients (four groups of 25), selected randomly and undergoing elective surgery, received atracurium 0.5 mg kg-1, with thiopentone, nitrous oxide and enflurane. Supplementary doses of fentanyl were given if needed. Train-of-four (TOF) stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height (T1) had recovered spontaneously to 10% of initial value, edrophonium 0.1, 0.2, 0.4 or 1 mg kg-1 was administered by random allocation. Enflurane concentrations remained constant, except that enflurane was discontinued in 50% of the patients who had received 2% enflurane. Monitoring was continued for at least 10 min, at which time T1 and TOF ratio (T4/T1) were measured. The ED80 for T1 recovery depended on the dose of enflurane: 0.08 (SEM 0.03), 0.21 (0.06) and 0.42 (0.18) mg kg-1 for 0%, 1% and 2% enflurane, respectively (P less than 0.005). With enflurane 2% discontinued, the ED80 was 0.095 (0.050) mg kg-1 (P less than 0.02 compared with 2% enflurane).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Pretreatment with non-depolarizing neuromuscular blocking agents and suxamethonium-induced increases in resting jaw tension in children.

We have studied the effect of prior administration of non-depolarizing neuromuscular blocking drugs on suxamethonium-induced increases in masseter muscle tension in 21 children aged 3-10 yr, anaesthetized with nitrous oxide and halothane using supramaximal stimulation of the ulnar nerve and the nerve to masseter. Resting tension and isometric force of contraction were measured in the adductor pollicis and masseter muscles. A sub-paralysing dose of tubocurarine 0.05 mg kg-1, a paralysing dose of atracurium 0.5 mg kg-1 or saline was given, followed 3 min later by suxamethonium 1 mg kg-1. Onset times of suxamethonium and atracurium block were shorter in the masseter than in the adductor pollicis muscle. When preceded by a sub-paralysing dose of tubocurarine, suxamethonium produced an increase in masseter tension (47 (SEM 15) g) similar to that produced by suxamethonium alone (59 (13) g). Prior administration of a paralysing dose of atracurium almost abolished this increase in tension (2.5 (2.5) g) (P less than 0.05 vs saline). The tension increase in adductor pollicis was 0, 3.2 (2.2) and 5.9 (1.1) g in the atracurium, tubocurarine and saline groups, respectively. Tubocurarine and atracurium prevented muscle fasciculations in all patients. It was concluded that increased muscle tone is a normal response to suxamethonium and is greater in the masseter than adductor pollicis. Sub-paralysing doses of non-depolarizing neuromuscular blockers have little effect, in contrast with paralysing doses. This suggests that the effect is mediated via postsynaptic receptors.

Ambulatory Surgical Procedures↗
PubMed1990

Comparison of double-burst and train-of-four stimulation to assess neuromuscular blockade in children.

Double-burst stimulation (DBS), a new technique to evaluate neuromuscular function, consists of two 50-Hz trains of 60-ms duration and 750 ms apart. DBS was compared with train-of-four (TOF) stimulation in 21 children aged 3-10 yr, during halothane anesthesia. On one arm the ulnar nerve was stimulated supramaximally with TOF stimulation every 12 s and the force of the evoked contraction of the adductor pollicis measured with an FTO3 force transducer and recorded on paper. Atracurium (0.4-0.5 mg.kg-1) was administered. During recovery from neuromuscular blockade, TOF stimulation was interrupted periodically and DBS substituted. The same stimulation patterns were applied to the ulnar nerve of the other arm simultaneously, and the clinical anesthesiologist was asked to estimate the degree of fade with both. There was good correlation between the measured TOF ratio (ratio of fourth to first response) and DBS ratio (ratio of second to first response). The TOF and DBS ratios above which fade could no longer be appreciated manually were (mean +/- SEM) 0.44 +/- 0.03 and 0.67 +/- 0.04 (P = 0.0002). Corresponding ranges were 0.3-0.8 for TOF and 0.4-0.9 for DBS, but DBS fade was always apparent if TOF fade could be detected. Therefore, in children, DBS is more sensitive than is TOF stimulation for the clinical assessment of recovery from neuromuscular blockade.

Anesthesia, Inhalation↗
PubMed1990

Vecuronium neuromuscular blockade at the diaphragm, the orbicularis oculi, and adductor pollicis muscles.

To determine the relationship among diaphragm, orbicularis oculi, and adductor pollicis blockade, train-of-four stimulation was applied to the phrenic, facial, and ulnar nerves in 16 adult patients anesthetized with alfentanil-propofol-oxygen. Vecuronium 0.04 or 0.07 mg/kg was given. The response of the adductor pollicis was measured with a force transducer, and that of the other muscles by electromyography (EMG). No statistically significant differences were detected with either dose in the intensity of maximum blockade measured at the three muscles. With 0.04 mg/kg, the first response (T1) in the train-of-four was decreased (mean +/- SEM) 78 +/- 8, 62 +/- 11, and 84 +/- 3% for the diaphragm, orbicularis oculi, and adductor pollicis, respectively. Corresponding values after 0.07 mg/kg were 95 +/- 3, 82 +/- 11, and 95 +/- 2%, respectively. However, onset time was longer at the adductor pollicis than at the diaphragm, and the orbicularis oculi onset time approached that of the diaphragm. With 0.04 mg/kg, time to maximum diaphragmatic blockade was 2.9 +/- 0.3 min, compared with 3.7 +/- 0.6 min at the orbicularis oculi (no significant difference [NS]) and 6.6 +/- 0.4 min at the adductor pollicis (P less than 0.001). With vecuronium 0.07 mg/kg the values were 2.2 +/- 0.3, 3.4 +/- 0.5 (P = 0.024), and 6.3 +/- 0.6 (P less than 0.001), respectively. Time to 75% T1 recovery was similar at the diaphragm and the orbicularis oculi, but significantly longer at the adductor pollicis.(ABSTRACT TRUNCATED AT 250 WORDS)

Diaphragm↗
PubMed1990

Clinical evaluation of double-burst stimulation. Its relationship to train-of-four stimulation.

Double-burst stimulation was compared with train-of-four stimulation in 23 adult patients receiving atracurium. Train-of-four was interrupted in 11 subjects every 2 minutes by one double-burst stimulation, and re-applied 6-30 seconds later; the height of the first double-burst response, compared with its control, was depressed slightly more than T1. The relationship between double-burst stimulation ratio and train-of-four ratio was indistinguishable from the line of identity. The train-of-four response, if repeated more than 12 seconds after double-burst stimulation, was not depressed compared with pre double-burst stimulation values. Fifteen anaesthetists were asked to detect fade manually in the second part of the study, while train-of-four was recorded on the opposite arm. One hundred and fourteen determinations were made in 12 patients. Fade was detected manually more often with double-burst stimulation than with TOF.

Atracurium↗
PubMed1990

Effect of d-tubocurarine pretreatment on succinylcholine twitch augmentation and neuromuscular blockade.

Subparalyzing doses of d-tubocurarine (dTC) given before succinylcholine decrease the duration of neuromuscular blockade. In animal preparations, they also abolish succinylcholine-induced twitch augmentation, defined as a greater-than-maximal contraction in response to a single stimulus. To determine quantitatively the effect of dTC on succinylcholine potency and on twitch augmentation in humans, 60 adult patients, ASA physical status I or II, were assigned randomly to receive either 0.05 mg/kg of dTC or saline 2 min before induction of anesthesia with fentanyl and thiopental. Train-of-four stimulation was applied every 12 s to the ulnar nerve and the force of contraction of the adductor pollicis muscle was measured. One minute after induction of anesthesia, 0.15, 0.20, 0.25, 0.35, or 0.50 mg/kg of succinylcholine was given. The height of the first twitch (T1) reached 121% +/- 6% (mean +/- SEM) of control without dTC, and was virtually abolished by dTC pretreatment (105% +/- 1%, P less than 0.01). Twitch augmentation was more noticeable with lower doses of succinylcholine, and was not observed in the response to the fourth stimulus of the train of four (T4). The potency of succinylcholine was decreased by approximately one-half in the dTC-pretreated groups. The ED50 was 0.27 +/- 0.04 mg/kg without dTC and 0.50 +/- 0.06 mg/kg with dTC (P less than 0.002). The corresponding values for ED90 were 0.51 +/- 0.07 and 1.02 +/- 0.12 mg/kg, respectively (P less than 0.02). The ED95 values were 0.63 +/- 0.09 and 1.28 +/- 0.15 mg/kg, respectively (P less than 0.02). The slopes of the regression lines did not deviate significantly from parallelism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Jaw muscle tension after succinylcholine in children undergoing strabismus surgery.

The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg.kg-1, during halothane anaesthesia were measured in eight children, 3-10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 +/- 23.2 g, mean +/- SD, at the jaw and 11.3 +/- 5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 +/- 33.4 g and 7.9 +/- 4.2 g, respectively. The duration of the phenomenon was 1-2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 +/- 6 sec--control groups; 39 +/- 11 sec--strabismus group, than at adductor pollicis, 61 +/- 34 sec--control groups; 75 +/- 28 sec--strabismus group (P less than 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children.

Anesthesia, Inhalation↗
PubMed1989

Cumulative dose-response curves for atracurium in patients with myasthenia gravis.

The potency of atracurium was determined in five patients with moderate to severe generalized myasthenia gravis undergoing thymectomy. Train-of-four stimulation was applied to the ulnar nerve and the force of contraction of the adductor pollicis was measured. Cumulative dose-response curves were obtained during thiopentone-nitrous oxide-fentanyl anaesthesia. The average time to complete the dose-response studies was 12.7 +/- 1.5 minutes. The ED50, ED90 and ED95 of atracurium were (mean +/- SEM) 0.07 +/- 0.01, 0.12 +/- 0.22, and 0.14 +/- 0.04 mg.kg-1, respectively. The time to 25 per cent first twitch recovery was 35 +/- 4 min following maximum blockade. Ten normal patients were studied in the same manner. Their ED50, ED90 and ED95 were 0.13 +/- 0.01, 0.21 +/- 0.02 and 0.24 +/- 0.03 mg.kg-1, respectively. These results demonstrated that, in patients with moderate to severe generalized myasthenia gravis, atracurium was 1.7-1.9 times as potent as in normal individuals.

Adult↗
PubMed1989

"Priming" with neostigmine: failure to accelerate reversal of single twitch and train-of-four responses.

Train-of-four stimulation can shorten the apparent onset time of neuromuscular blocking drugs. This study was designed to verify whether the same occurred with neostigmine-assisted recovery, and whether this apparent acceleration could explain the previously reported effectiveness of the priming technique for reversal agents. Fourteen adults received atracurium, 0.5 mg.kg-1, during a thiopentone-nitrous oxide-enflurane anaesthetic. The ulnar nerves of both arms were stimulated with train-of-four stimulation every 12 seconds until 1 per cent recovery of first twitch, at which time stimulation in one arm was switched to single twitch. When mean first twitch height reached 10 per cent of control, neostigmine, 0.04 mg.kg-1, was administered either as a single bolus, or as a "priming" dose of 0.01 mg.kg-1, followed 3 min later by 0.03 mg.kg-1. No statistically significant differences were observed between single twitch in one arm and first twitch height of the train-of-four in the other arm for the next 10 min. With priming, first twitch height was 45 +/- (SEM) 5 per cent at 5 min and 85 +/- 6 per cent at 10 min, compared with 72 +/- 5 per cent (p less than 0.05) and 91 +/- 2 per cent (NS) respectively without priming. Train-of-four ratio was 28 +/- 3 per cent at 5 min and 65 +/- 5 per cent at 10 min with priming, versus 53 +/- 4 per cent (P less than 0.05) and 73 +/- 3 per cent (NS) respectively without priming.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗
PubMed1989

Dose-response relationships for edrophonium and neostigmine as antagonists of atracurium and vecuronium neuromuscular blockade.

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.

Atracurium↗
PubMed1989

Differential effects of pancuronium on masseter and adductor pollicis muscles in humans.

The sensitivity of the masseter, one of the muscles of the upper airway, to pancuronium was measured in ten adults undergoing elective surgery and compared with that of the adductor pollicis. During thiopental-nitrous oxide-enflurane (end-tidal concentration less than 0.25%) anesthesia, supramaximal nerve stimulation was applied to the ulnar nerve at the elbow and to the nerve to the masseter, at a point inferior to the zygomatic arch, anterior to the mandibular condyle. Jaw closure was measured by a force transducer system attached to both an oral airway and a metal frame fixed to the operating table 10 cm caudad to the chin. Cumulative dose-response curves for pancuronium (initial dose = 0.02 mg/kg, incremental doses = 0.01 mg/kg) were determined. Control twitch tensions were (mean +/- SEM) 473 +/- 75 g at the masseter and 660 +/- 118 g at the adductor pollicis. The masseter was slightly more sensitive to pancuronium, the ED50 being 0.024 +/- 0.001 mg/kg compared with 0.028 +/- 0.001 mg/kg for the adductor pollicis (P less than 0.05). Corresponding values for the ED90 were 0.038 +/- 0.004 and 0.043 +/- 0.002 mg/kg, respectively (P less than 0.05). The time from injection of the first dose of pancuronium to maximum blockade was 3.2 +/- 0.2 min at the masseter and 3.8 +/- 0.2 min at the adductor pollicis (P less than 0.01). Following incremental doses, this time was 1.8 +/- 0.1 and 2.6 +/- 0.1 min, respectively (P less than 0.01). It is concluded that after injection of pancuronium, neuromuscular blockade is greater at the masseter and occurs sooner than at the adductor pollicis. Jaw relaxation can be achieved with relatively small doses of pancuronium. This suggests that return of adductor pollicis function may not imply complete masseter muscle recovery.

Adult↗
PubMed1989

[Therapeutic difficulties in discontinuous absence-petit mal status].

After a change in her antiepileptic medication, a 29 year old woman, who had petit mal absences since childhood, developed an intoxication by phenobarbital and a intermittent absence status. The intravenous administration of clonazepam paradoxically produced a transitory increase of the spike-wave-activity. Only 8 days later, when the serum level of phenobarbital had dropped and the concentration of valproic acid and ethosuximide were near the "therapeutic range", did the absences remit.

Adult↗
PubMed1989

Effects of succinylcholine at the masseter and adductor pollicis muscles in adults.

The effect of succinylcholine on baseline tension and evoked twitch height was measured at the masseter and the adductor pollicis muscles in ten adults undergoing elective surgery. During thiopental-nitrous oxide-enflurane (end-tidal concentration less than 0.25%) anesthesia, supramaximal stimulation was applied to both the ulnar nerve and the nerve to the masseter. Baseline tension and the isometric force of contraction were measured at the jaw and the thumb. Cumulative dose-response relationships were obtained by giving succinylcholine in incremental doses (initial dose, 0.10 mg/kg, followed by 0.05- or 0.1-mg/kg increments, depending on response). An infusion was started after the maximum effect of the first dose, at a rate adjusted to compensate for the rapid metabolism of the drug. There was no difference between the sensitivity of the masseter and the adductor pollicis. The ED50 values were (mean +/- SEM) 0.11 +/- 0.01 mg/kg at both muscles. The ED90 values were 0.17 +/- 0.02 mg/kg at the masseter and 0.16 +/- 0.01 mg/kg at the adductor pollicis. Onset of action was more rapid at the masseter. In six of the ten patients, baseline tension at the jaw was found to increase by a mean of 80 +/- 24 g (range 25-188 g). It is concluded that in adults, masseter neuromuscular blockade can be achieved with succinylcholine doses approximately equal to those required to block the adductor pollicis. In addition, the drug may cause increased tension in the muscles of the jaw.

Adult↗