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Biomedical subjects

F Donati

Publications and source records attributed to F Donati.

At least 109 records · Page 6Linked to original sources

Respiratory mechanics in anaesthetised patients after neostigmine-atropine. A comparison between patients with and without chronic obstructive pulmonary disease.

The aim of this study was to compare the effects of pharmacological reversal of neuromuscular blockade on static compliance and resistance in patients with and without chronic obstructive pulmonary disease (COPD). Twenty patients were studied: 12 patients were free of respiratory disease (NCOPD) and had normal pulmonary function tests. Eight subjects (COPD) had a clinical history of chronic bronchitis and a FEV1 < 70% of the predicted value. All patients were anaesthetised with a continuous infusion of methohexitone and alfentanil. Airway pressure (Paw) was recorded continuously. Static compliance (Crs) was calculated from the relationship between 21 syringe volume (250 ml step) and Paw. Total respiratory resistance (Rrs) was measured at two levels of inspiratory flow and tidal volume. These measurements were made before vecuronium (control), after injection of vecuronium to abolish the first neuromuscular response to train of four, 5 and 15 min after administration of neostigmine 40 micrograms.kg-1 and atropine 10 micrograms.kg-1. In COPD patients Crs and Rrs were significantly greater (1450 +/- 580 ml.kPa-1 and 1.06 +/- 0.68 kPa.l-1.s-1) than in normal patients (1000 +/- 380 ml.kPa-1 and 0.58 +/- 0.22 kPa.l-1.s-1) (P < 0.01). In both groups Crs and end-expiratory pulmonary volume were similar before injection of vecuronium and after neostigmine-atropine administration. In both groups, Rrs was not altered significantly by neostigmine-atropine for the two inspiratory flows. These results suggest that neostigmine-atropine mixture is associated with small changes in respiratory mechanics, and the changes are similar in COPD compared with normal patients.

Airway Resistance↗

Impact of prematurity and intrauterine growth retardation on neonatal hemorrhagic and ischemic brain damage.

Low birth weight and intrauterine growth retardation are well-recognized risk factors for increased mortality, morbidity and poor neurologic outcome. Risk assessment is different considering true preterm (appropriate-for-gestational-age, AGA) or growth-retarded (small-for-gestational-age, SGA) infants. Therefore, we carried out a study on the incidence of hemorrhagic (peri-intraventricular hemorrhage, PIVH) and ischemic (periventricular leukomalacia) brain lesions in two groups of AGA and SGA very-low-birth-weight (VLBW) infants. In the study period (1987-1990), 111 VLBW babies (< 1,500 g body weight) were serially studied at days 1, 3 and 7 and weekly until discharge by cerebral ultrasonography (ATL, MK 4, 7.5 MHz). 57 were VLBW-AGA babies (mean gestational age 28 weeks, mean body weight 1,106 g). 54 were VLBW-SGA babies (mean gestational age 31 weeks, mean body weight 990 g). PIVH was graded according to the system of Papile et al. Periventricular leukomalacia was defined as an echodensity (> 3 mm) adjacent to the lateral border of the ventricular body. We noted a higher incidence of PIVH in the AGA group (36.8%) than in SGA babies (18.5%; p < 0.01, Fisher test). The AGA subgroup < 1,000 g body weight had 72.2% PIVH compared to AGA babies > 1,000 g (20.5%; p < 0.01). The same relationship was observed in SGA babies (34.8% in < 1,000 g and 6.4% in > 1,000 g babies). Ischemic brain lesions (periventricular leukomalacia) were equally distributed between AGA and SGA babies (10.5 vs. 3.7%, p > 0.5) independently of body weight category.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Damage, Chronic↗

The orbicularis oculi and the adductor pollicis muscles as monitors of atracurium block of laryngeal muscles.

The aim of this study was to determine whether atracurium-induced neuromuscular block at the laryngeal adductor muscles could be predicted by visual inspection of either adductor pollicis or orbicularis oculi responses. Twenty-one ASA Class I or II patients were anesthetized with propofol (2-2.5 mg/kg) and fentanyl (2-5 micrograms/kg). Tracheal intubation was performed without neuromuscular blocking drugs. Patients were assigned randomly to receive atracurium 0.3 or 0.5 mg/kg intravenously. Train-of-four stimulation was applied to the ulnar, facial, and recurrent laryngeal nerves. Laryngeal response was measured as the pressure change in the tracheal tube cuff positioned between the vocal cords. The response at the adductor pollicis and orbicularis oculi was evaluated visually by two observers who detected if and when block was complete. Twelve patients, including all those receiving 0.5 mg/kg, had complete orbicularis oculi block. The same patients, except one, also had 100% laryngeal block. Adductor pollicis response was abolished in the same 12 patients plus an additional 4 patients. In patients receiving atracurium 0.5 mg/kg, laryngeal and orbicularis oculi responses were abolished faster (mean +/- SD: 132 +/- 80 and 146 +/- 58 s, respectively) than the adductor pollicis muscle (243 +/- 55 s; P < 0.05). There was a significant correlation (r = 0.94; P < 0.001) between neuromuscular block onset time at the laryngeal adductor and orbicularis oculi muscles but not between laryngeal and thumb muscles. The authors conclude that, after injection of atracurium, laryngeal adductor and orbicularis oculi blocks have similar intensities and time courses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Importance of early blood sampling on vecuronium pharmacokinetic and pharmacodynamic parameters.

The effect of early blood sampling on the description of the vecuronium pharmacokinetic-pharmacodynamic relationship was studied following a bolus injection. Sample collection every 10 sec during the first 2 min showed a high concentration peak at 30 to 40 sec, accounting for an important proportion of the total area under the plasma concentration-time curve (AUC). Neglecting it, using only blood samples drawn at 1 and 2 min (limited sampling), led to a significant overestimation of noncompartmentally derived values of mean residence time, clearance, volume of distribution at steady-state and rate of transfer of vecuronium into the effect compartment. Compartmental pharmacokinetics could not be applied to concentration-time curves constructed with early samples, but limited sampling data were fitted to a 2-compartment model. Derived compartmental pharmacokinetic and pharmacokinetic-pharmacodynamic parameters were similar to those obtained noncompartmentally with complete sampling every 10 sec, because back-extrapolation to time zero contributed to the increase in the AUC. However, compartmental analysis does not provide an accurate description of concentration changes following injection.

Adult↗

Speed of action of various muscle relaxants at the neuromuscular junction binding vs. buffering hypothesis.

The speed of action of several nondepolarizing muscle relaxants (gallamine, rocuronium, D-tubocurarine, atracurium, vecuronium, pancuronium and doxacurium) was tested iontophoretically at the frog cutaneous pectoris neuromuscular junction at various temperatures. If differences in rate of onset and offset are due to different molecular rates of binding (and unbinding), and of resulting conformational changes, they should be strongly temperature dependent. In contrast, if differences are due to differences in buffered diffusion, temperature dependence should be low to moderate. The onset and recovery time constants of inhibition of brief acetylcholine pulses, caused by long pulses of relaxants for all of the muscle relaxants, were inversely related to apparent dissociation constants (KD values), that ranged from 4.56 microM (gallamine) to 0.11 microM (doxacurium). The kinetics showed only modest temperature dependence (Q10 values of 1/time constant of offset were typically < 1.4). Because KD values of all muscle relaxants were even less temperature dependent (Q10 < 1.3), this suggests that the kinetics of inhibition is probably determined by the extent of buffering in the synaptic cleft, and not by binding and unbinding. Diffusion of relaxants from the synaptic cleft is expected to be strongly buffered, because the nerve terminal presents a physical barrier to diffusion, and because of extremely high density of acetylcholine receptors. The density of acetylcholine receptors can be calculated from the time constant of offset and KD values of various relaxants, assuming that buffer diffusion is determining the kinetics of action of muscle relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High-performance liquid chromatography-electrochemical detection of vecuronium and its metabolites in human plasma.

A high-performance liquid chromatographic assay coupled with electrochemical detection has been developed for the determination of vecuronium and its three putative deacetylated metabolites in human plasma. A novel solid-phase extraction procedure allowed good recovery of both vecuronium and its metabolites, together with ease and speed of execution. This method was sensitive, reproducible and accurate over the therapeutic range of concentrations of vecuronium and its metabolites, and was applied successfully to a study of the pharmacokinetics of vecuronium in anaesthetized patients.

Chromatography, High Pressure Liquid↗

Rocuronium (ORG 9426) neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis in humans.

The effects of rocuronium, 0.25 or 0.5 mg.kg-1, were measured simultaneously on the adductor muscles of the larynx and adductor pollicis in 14 adult patients. Anaesthesia was induced and maintained with propofol and fentanyl. Tracheal intubation was performed without muscle relaxants. The recurrent laryngeal and ulnar nerves were both stimulated supramaximally, at the notch of the thyroid cartilage and at the wrist respectively, using train-of-four stimulation. The laryngeal response was evaluated by measuring the pressure change in the cuff of a tracheal tube positioned between the vocal cords. Onset time, intensity of blockade and duration of action were less at the larynx than at the adductor pollicis. After rocuronium, 0.25 mg.kg-1, the onset time (interval between injection and maximal T1 blockade) was 1.6 +/- 0.1 min and 3.0 +/- 0.3 min (mean +/- SEM) at the laryngeal muscles and adductor pollicis, respectively (P less than 0.01 between muscles). Maximum blockade was 37 +/- 8% and 69 +/- 8%, respectively (P less than 0.05), and time to 90% T1 recovery was 7 +/- 1 min and 20 +/- 4 min, respectively (P less than 0.05). With 0.5 mg.kg-1, the onset time was also more rapid at the vocal cords (1.4 +/- 0.1 min) than at the adductor pollicis (2.4 +/- 0.2 min, P less than 0.001). Maximum blockade was 77 +/- 5% and 98 +/- 1%, respectively (P less than 0.01), and time to 90% T1 recovery was 22 +/- 3 min and 37 +/- 4 min, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intracranial lipomas.

Intracranial lipomas are very rare tumors, mostly being localized in the midline and often asymptomatic. We report on three children with intracranial lipomas (one with extension to the cervical spinal cord) diagnosed by CT and/or MR. All three had different symptoms and neurological signs. We summarize the case reports in the literature since the CT-era.

Brain Neoplasms↗

Iontophoretic study of speed of action of various muscle relaxants.

The speed of action of nondepolarizing muscle relaxants is inversely related to potency. The hypothesis that this effect occurs at the end plate was tested in a frog (Rana pipiens) cutaneous pectoris muscle preparation. Brief acetylcholine pulses (10-100 ms) were applied iontophoretically from a central barrel of a triple-barrelled microelectrode located near an end plate. Long pulses (10-200 s) of muscle relaxant (gallamine, rocuronium, d-tubocurarine, atracurium, vecuronium, pancuronium, and doxacurium) were applied from one of two other barrels. The responses were a voltage change at the end plate, measured with an intracellular electrode. To evaluate potency, intracellular voltage changes following iontophoretic acetylcholine pulses were measured after application of various concentrations of muscle relaxants. The following were the equilibrium dissociation constants, which represent concentration of relaxant for 50% inhibition of response (mean plus or minus standard deviation): gallamine, 4.56 +/- 0.44 microM (n = 5); rocuronium, 0.71 +/- 0.09 microM (n = 6); d-tubocurarine, 0.59 +/- 0.07 microM (n = 4); atracurium, 0.31 +/- 0.03 microM (n = 4); vecuronium, 0.23 +/- 0.02 microM (n = 5); pancuronium, 0.18 +/- 0.03 microM (n = 3); doxacurium, 0.11 +/- 0.03 microM (n = 5). Both onset and offset of effect of muscle relaxant proceeded with an exponential time course.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstanols↗

Dose-response relations of doxacurium and its reversal with neostigmine in young adults and healthy elderly patients.

Dose-response relationships for doxacurium and neostigmine were established in 24 young (18-40 yr) and 24 elderly (70-85 yr) patients, ASA physical status I or II, anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. Mechanomyographic response of the adductor pollicis muscle to the train-of-four stimulation of the ulnar nerve was recorded. Doxacurium (5, 10, 15, or 20 micrograms/kg IV) was administered by random allocation. After maximal blockade, and additional dose, for a total of 30 micrograms/kg, was administered. When first twitch height recovered to 25%, incremental doses of 5 micrograms/kg were administered for maintenance of relaxation. Neostigmine (5, 10, 20, or 40 micrograms/kg) was injected at 25% first twitch recovery, and neuromuscular monitoring was continued for 10 min. The doses of doxacurium (+/- SEM) required to produce a 50%, 90%, and 95% depression of twitch tension in the young patients were, respectively, 13.3 +/- 1.6, 23.6 +/- 2.8, and 28.6 +/- 3.4 micrograms/kg, not statistically different from corresponding values in the elderly, 11.8 +/- 1.3, 21.2 +/- 2.3, and 25.9 +/- 2.9 micrograms/kg, respectively. Time to 25% recovery after 30 micrograms/kg was 80.2 +/- 12.2 min in the young versus 133.0 +/- 17.1 min in the elderly (P less than 0.05). Neostigmine-assisted recovery was not significantly different in both groups. The estimated doses of neostigmine to obtain 70% train-of-four recovery after 10 min were 53.6 +/- 7.5 micrograms/kg in the young and 41.6 +/- 5.8 micrograms/kg in the elderly (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Neurological complications following tonsillectomy].

Iatrogenic neurological complications of tonsillectomy have been extremely rarely described. We report on 5 patients who developed glossopharyngeal paresis, impairment of taste on the base of the tongue, or hypoglossal paresis following tonsillectomy, and discuss the possible etiology of these isolated lesions of the cranial nerves.

Adult↗

[Variability of epileptic seizure phenomenology in infants and children].

It is well known that some patients may have two or more different types of seizures. Partial epilepsies and more than 15 different epileptic syndromes (e.g. West or Lennox-Gastaut syndrome or epilepsies with absences) can lead to the intraindividual manifestation of two or more seizure types. Among 728 children with epilepsy seen at the outpatient department 9.1% had two different types of seizures and 1.5% had more than two types of seizures. The most common association observed was between tonic-clonic seizures and absences. The most frequently observed epileptic syndromes were in decreasing order: multifocal epilepsies, epilepsies with absences, Lennox-Gastaut syndrome and West syndrome. The association of two or more different seizure types in the same patient seems to be a negative prognostic factor.

Child↗

[Prognostic value of the EEG prior to the start and the discontinuation of anticonvulsive therapy].

Opinions are divided about the prognostic value of the EEG in the course of epilepsy. We thus prospectively examined 275 children with epilepsy; in particular, we analyzed the prognostic role of the EEG. Out of these 275 children 209 (76%) have been free from attacks for more than one year. In 107 children the anticonvulsive therapy was discontinued, leading to a relapse rate of 27%. According to our results, only the focal EEG changes, up to interruption of the anticonvulsive therapy, show a statistical significance in the course of epilepsy. On the other hand, a normal EEG before or normalization of the EEG after commencement of therapy and also the absence of any epileptic activity (focal or generalized), are likely to be favourable. However, we could not find a statistically significant difference.

Adolescent↗

A kinetic-dynamic model to explain the relationship between high potency and slow onset time for neuromuscular blocking drugs.

To account for experimental data showing increased onset time with increased potency of neuromuscular blocking drugs, a pharmacokinetic-pharmacodynamic model is presented. It is characterized by a finite concentration of receptors (R) in the effect compartment. Transfer from central to effect compartment is linearly related to concentration gradient. A sigmoid Emax model is used to describe the relationship between receptor occupancy and effect. Plasma concentrations found in the literature are used. Differential equations are solved numerically for equipotent doses of drugs of different potencies. Because the density of receptors constitutes a significant drain of drug molecules for potent drugs, the model predicts an inverse relationship between speed of onset and potency. The concentration of receptors in the effect compartment R which best fits experimental data obtained in humans is 0.28 mumol/L. With this value of R, onset times are prolonged when the ED95 (dose for 95% blockade) is less than 0.1 mumol/kg. It is concluded that, in the development of a short-acting nondepolarizing neuromuscular blocking drug, agents having an ED95 of 0.1 mumol/kg or greater appear more promising.

Dose-Response Relationship, Drug↗