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F Donati

Publications and source records attributed to F Donati.

At least 37 records · Page 2Linked to original sources
PubMed2001

Peripheral link model as an alternative for pharmacokinetic-pharmacodynamic modeling of drugs having a very short elimination half-life.

Attempts to obtain estimates of pharmacokinetic-pharmacodynamic (PK-PD) parameters for mivacurium with traditional central link models were unsuccessful in many patients. We hypothesized that a link model with the peripheral compartment would be more appropriate for mivacurium in view of its extremely rapid plasma clearance and its potential elimination by tissue pseudocholinesterases. For validation purposes, the peripheral link model was applied to other neuromuscular blocking agents (NMBA), i.e., atracurium and doxacurium which have respectively an intermediate and a long elimination half-life. Assuming peripheral elimination in PK-PD modeling was investigated but found to have no impact on the estimation of PK-PD parameters. Our results indicate that, for drugs having intermediate and long elimination half-lives, EC50 values are similar with either the central or peripheral link model. For mivacurium, a peripheral link model enables PK-PD modeling in all subjects, with more precision in the PK-PD parameter estimates and a better fitting of the effect data when compared to the central link model. For these reasons, a peripheral link model should be preferred for mivacurium.

Adolescent↗
PubMed2001

The corrugator supercilii, not the orbicularis oculi, reflects rocuronium neuromuscular blockade at the laryngeal adductor muscles.

BACKGROUND: Some studies suggest that the orbicularis oculi is resistant to neuromuscular blocking drugs and behaves like laryngeal muscles. Others report little or no difference between the orbicularis oculi and the adductor pollicis. These discrepancies could be related to the exact site of recording. The purpose of this study was to compare two monitoring sites around the eye with the adductor pollicis and the laryngeal adductor muscles. METHODS: After institutional approval and informed consent, the evoked response to train-of-four stimulation was measured in 12 patients by acceleromyography at the thumb (adductor pollicis), the eyelid (orbicularis oculi), and the superciliary arch (corrugator supercilii) after 0.5 mg/kg rocuronium during propofol-fentanyl-nitrous oxide anesthesia. In 12 other patients, laryngeal adductor neuromuscular blockade was assessed via the cuff of the tracheal tube and compared with the adductor pollicis and the corrugator supercilii after 0.6 mg/kg rocuronium. RESULTS: After 0.5 mg/kg, maximum blockade (%T1, mean +/- SD) was less at the corrugator supercilii (80+/-20%) than at the adductor pollicis (100+/-1%) and the orbicularis oculi (93+/-8%) (P < 0.01). Clinical duration (25%T1) was shorter at the corrugator supercilii (12+/-7 min) than at the adductor pollicis (25+/-4 min) and orbicularis oculi (24+/-10 min) (P < 0.01). After 0.6 mg/kg, maximum blockade was similar at the corrugator supercilii (88+/-8%) and the laryngeal adductor muscles (89+/-11%). Clinical duration at the corrugator supercilii and the laryngeal adductors was 17+/-7 and 17+/-10 min, respectively. CONCLUSIONS: Muscles around the eye vary in their response to rocuronium. The response of the superciliary arch (corrugator supercilii) reflects blockade of laryngeal adductor muscles. However, the eyelid (orbicularis oculi) and thumb (adductor pollicis) have similar sensitivities.

Adolescent↗
PubMed2001

Increased sensitivity to depolarization and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms.

BACKGROUND: Newborn neuromuscular junctions are more sensitive to d-tubocurarine than more mature preparations. It is unclear whether the same modifications occur with newer nondepolarizing agents and depolarizing agent succinylcholine. The purpose of this study was to determine the relative sensitivity of newborn neuromuscular junctions to succinylcholine and five nondepolarizing agents. METHODS: The phrenic nerve-hemidiaphragm preparation from 60 rats was used, 30 aged 9-12 days (newborn) and 30 aged 27-33 days (adult). Five rats from each group were exposed to one of six neuromuscular blocking agents (d-tubocurarine, cisatracurium, atracurium, vecuronium, rocuronium, and succinylcholine). Indirectly elicited twitch tension was measured during control conditions in the absence of blocking agent, followed by four concentrations of one of the six agents. Concentration-response curves were constructed and the EC50 (concentration required to produce 50% depression of twitch tension) was obtained. Potency ratios (EC50adult/EC50newborn) were derived for each agent. RESULTS: Newborn preparations were significantly (P < 0.001) more sensitive than their adult counterparts for all six agents tested. For nondepolarizing agents, the potency ratio was in the 6-12 range. The EC50adult/EC50newborn were as follows, in decreasing potency order: d-tubocurarine, 1.68/0.23 microM; cisatracurium, 2.73/0.47 microM; vecuronium, 5.47/0.59 microM; rocuronium, 9.7/0.78 microM; and atracurium, 12.3/1.9 microM. Succinylcholine was three times as potent in newborn rats, with an EC50adult/EC50newborn of 21.3/7.3 microM. The ratio for succinylcholine was significantly less than for all nondepolarizing drugs (P < 0.02). CONCLUSION: The newborn neuromuscular junction of the rat shows an increased sensitivity to all neuromuscular blocking agents tested, including succinylcholine. However, the potency ratio was greater for nondepolarizing than depolarizing drugs. The optimal dose of these agents for certain situations such as cesarean section and anesthesia in neonates should be reassessed.

Animals↗
PubMed2001

Radiofrequency thermal ablation of hepatocellular carcinoma: using contrast-enhanced harmonic power doppler sonography to assess treatment outcome.

OBJECTIVE: We evaluated the accuracy of contrast-enhanced harmonic power Doppler sonography in assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma. SUBJECTS AND METHODS: Fifty patients with 65 hepatocellular carcinoma nodules (1-5 cm in diameter; mean diameter, 2.5 cm) were studied using unenhanced and contrast-enhanced harmonic power Doppler sonography before and after IV administration of a microbubble contrast agent. The examinations were repeated after treatment of the tumors with radiofrequency ablation. Findings of the Doppler studies were compared with those of dual-phase helical CT, which were used as points of reference for assessing treatment outcome. RESULTS: Before radiofrequency treatment, intratumoral blood flow was revealed by unenhanced power Doppler sonography in 48 (74%) of 65 hepatocellular carcinoma nodules. After injection of the contrast agent, intratumoral enhancement was observed in 61 (94%) of 65 hepatocellular carcinomas (p < 0.01). After radiofrequency treatment, all 51 (84%) of the 61 hepatocellular carcinomas found to be necrotic on helical CT scans failed to show enhancement on power Doppler sonograms. In nine of the 10 lesions that showed a residual viable tumor on helical CT scans, persistent intratumoral enhancement-matching the enhancing areas on helical CT images-was revealed by power Doppler sonography. These nine hepatocellular carcinomas were subjected to repeated radiofrequency thermal ablation with the guidance of contrast-enhanced power Doppler sonography. Complete necrosis was seen after the second treatment session in six of the nine lesions. CONCLUSION: Contrast-enhanced harmonic power Doppler sonography is an accurate technique for assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma and may be useful in guiding additional treatment in patients with incomplete response to initial efforts.

Aged↗
PubMed2001

A multicenter evaluation of the time-course of action of two doses of rapacuronium after early and late reversal with neostigmine.

UNLABELLED: Early reversal of rapacuronium may accelerate return of neuromuscular function. This study was designed to compare early (2 min after rapacuronium) or late (at 25% recovery of the first twitch [T1] of train-of-four) reversal of rapacuronium with neostigmine. We studied 119 subjects between the ages of 18 and 75 yr. Anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide, propofol, and fentanyl. Mechanomyographic neuromuscular monitoring was performed by using train-of-four stimulation of the ulnar nerve. Two groups received 1.5 mg/kg rapacuronium followed by neostigmine (50 microg/kg) and glycopyrrolate (10 microg/kg) either at 2 min after rapacuronium bolus or at 25% T1 recovery. The other two groups received 2.0 mg/kg rapacuronium, after which neostigmine was similarly given. For each rapacuronium dose, the time from the administration of rapacuronium to the start of T1 recovery or 25% T1 recovery was significantly shorter in subjects who received the reversal 2 min after rapacuronium. However, late recovery, defined by times from administration of rapacuronium to 70%, or 80% T4/T1 recovery, was not influenced by early reversal administration. We conclude that initial recovery is accelerated by early administration of neostigmine. Time to full recovery after rapacuronium administration is, however, dose-dependent and not significantly altered by early administration of neostigmine. IMPLICATIONS: "Rescue reversal," which includes the administration of neostigmine shortly after the administration of rapacuronium, may accelerate the return of spontaneous breathing (early recovery), but does not shorten the time to complete recovery of upper airway function.

Adolescent↗
PubMed2000

SPECT during sleepwalking.

Sleepwalking is a dissociation between body sleep and mind sleep. We report single photon emission computed tomography (SPECT) in a man with a history of sleepwalking. Our findings suggest that this dissociation arises from activation of thalamocingulate pathways and persisting deactivation of other thalamocortical arousal systems.

Adolescent↗
PubMed2000

Intubating conditions and blockade after mivacurium, rocuronium and their combination in young and elderly adults.

PURPOSE: Mivacurium-rocuronium combinations have been demonstrated to be more potent than either drug given alone. Combinations were compared with mivacurium and rocuronium, with respect to onset, intubating conditions, and duration of action in young and elderly adults. METHODS: Fentanyl-propofol-N2O-isoflurane anesthesia was given to ASA I and II adults aged 18-65 yr (45 patients) and over 66 yr (45 patients). In this blinded randomized study, we compared accelerographic adductor pollicis response and visual assessment of response to facial nerve stimulation after 0.25 mg x kg(-1) mivacurium, 0.6 mg x kg(-1) rocuronium, and a combination of 0.08 mg kg(-1) mivacurium plus 0.2 mg x kg(-1) rocuronium. Intubating conditions at 2.5 min were rated as excellent, good, fair or poor. RESULTS: Onset times were similar for all drugs regimens and for both age groups (204-276 sec at the thumb; 142-196 sec at the eye) (P<0.05 between muscles). Intubating conditions were similar in all groups, and rated good or excellent, except in two subjects. In young patients duration to 25% recovery was longer (P<0.05) for rocuronium (mean +/- SD) (39+/-11 min) than for either mivacurium (23+/-6 min), or the combination (27+/-7 min). Duration was prolonged in the elderly for rocuronium (54+/-17 min), and the combination (35+/-11 min), but not for mivacurium (24+/-6 min). CONCLUSIONS: Mivacurium-rocuronium combinations yield onset times and intubating conditions similar to either parent agent with only two thirds as much total drug. Duration for such a mixture is similar to that of mivacurium in young adults and slightly prolonged in the elderly.

Adult↗
PubMed2000

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children.

PURPOSE: To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children. METHODS: We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (TI 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteady-state during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion. RESULTS: Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean +/- SD: 330 +/- 42 ng x ml(-1); 127 +/- 27 ng x ml(-1); P < 0.001); similarly the clearances showed a bimodal distribution (mean +/- SD: 5.08 +/- 0.94; 11.51 +/- 0.2 ml x min(-1) x kg(-1) P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05). CONCLUSION: Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.

Anesthesia↗
PubMed2000

MnDPDP-enhanced MRI vs dual-phase spiral CT in the detection of hepatocellular carcinoma in cirrhosis.

The objectives of this study were twofold: (a) to assess safety and tolerability of the hepatobiliary MR contrast agent MnDPDP; and (b) to investigate the sensitivity of MnDPDP-enhanced MRI, in comparison with dual-phase spiral CT, in the detection of hepatocellular carcinoma (HCC) in cirrhosis. Fifty patients with liver cirrhosis and histologically proven HCC were enrolled in a prospective phase-IIIB clinical trial. All patients underwent evaluation with dual-phase spiral CT and pre-contrast and post-contrast MRI at 1.5 T. The MR examination protocol included spin-echo (SE) and gradient-recalled-echo (GRE) T1-weighted images acquired before and 60-120 min after administration of 0.5 micromol/kg (0.5 ml/kg) MnDPDP (Teslascan, Nycomed Amersham, Oslo, Norway); and fast T2-weighted SE images obtained solely before contrast injection. Gold standard was provided by findings at Lipiodol CT in combination with follow-up spiral CT studies, which were repeated at 4-month intervals over a 10- to 27-month (mean +/- SD 20.1 +/- 5.1 months) follow-up period. No serious adverse event occurred. Eighty tumors ranging 0.8-9.1 cm in diameter (mean +/- SD 3.2 +/- 2.4 cm) were detected by Lipiodol CT or confirmed as cancerous foci by follow-up CT studies. Pre-contrast MRI detected 38 of 80 lesions (48%); MnDPDP-enhanced MRI, 65 of 80 lesions (81%); pre-contrast plus post-contrast MRI, 69 of 80 lesions (86%); and dual-phase spiral CT, 64 of 80 lesions (80%). The difference between unenhanced and MnDPDP-enhanced MRI was statistically significant (p < 0.001). The difference between MRI (pre-contrast plus post-contrast) and dual-phase spiral CT was not statistically significant (p = 0.33). The confidence in the final diagnosis, however, was significantly higher for MRI as compared with spiral CT (p<0.001). MnDPDP is a safe and well-tolerated hepatobiliary MR contrast agent. Magnetic resonance imaging with use of MnDPDP is significantly more sensitive than unenhanced MRI and as good as dual-phase spiral CT for detection of HCC in cirrhosis.

Carcinoma, Hepatocellular↗
PubMed2000

Postanoxic alpha (theta) coma: a reappraisal of its prognostic significance.

OBJECTIVES: To appraise the controversial prognostic significance of postanoxic alpha or theta coma (ATC). METHODS: We prospectively assessed 14 comatose patients with ATC after cardiac arrest by means of a protocol which included repeated clinical examinations, EEG, and median somatosensory evoked potentials (SEP). Good outcome was defined by the reappearance of cognition (Glasgow outcome scale 3-5) at any time during the 1 year follow-up. RESULTS: Nine of 14 patients had a monotonous, frontally accentuated and a reactive alpha (theta) EEG activity (complete ATC). In these patients ATC was recorded a mean of 47 h after resuscitation, the mean Glasgow coma scale (GCS) was 4 at 48 h, and early cortical SEPs were altered or absent in 5 of 7 patients. All nine patients died. In five of 14 patients the alpha (theta) EEG activity was either not monotonous, partially reactive or posteriorly dominant (incomplete ATC). In these patients ATC was recorded a mean of 43 h after resuscitation, the mean GCS was 8 at 48 h, and early cortical SEP were normal in 4 of 5 patients. Three of 5 patients regained cognition, two of them remained however dependent in activities of everyday life. CONCLUSIONS: This study and a review 283 cases of postanoxic ATC reported in the literature suggest the existence of incomplete and complete variants of postanoxic ATC. Whereas complete ATC is invariably associated with a poor outcome, full recovery is possible in patients with incomplete ATC. The combination of EEG, clinical, and SEP findings improves the prognostic accuracy of postanoxic ATC.

Adult↗
PubMed2000

Pharmacokinetic studies of neuromuscular blocking agents: good clinical research practice (GCRP).

In September 1997, an international consensus conference on standardization of studies of neuromuscular blocking agents was held in Copenhagen, Denmark. Based on the conference, a set of guidelines for good clinical research practice (GCRP) in pharmacokinetic studies of neuromuscular blocking agents is presented. Guidelines include: design of the study; relevant patient groups to investigate; test drug administration, sampling and analysis; pharmacokinetic analysis; pharmacokinetic/pharmacodynamic modeling; population pharmacokinetics; statistics; and presentation of pharmacokinetic data. The guidelines are intended to aid those working in this research area; it is hoped that they will assist researchers, editors of scientific papers, and pharmaceutical companies in improving the quality of pharmacokinetic studies.

Body Temperature↗
PubMed2000

Update on perinatal hypoxic insult: mechanism, diagnosis and interventions.

Cerebral hypoxia-ischaemia in the neonate can produce irreversible tissue injury and is always associated with major perturbations in the energy status of the brain. The major neurological manifestations of brain injury in these babies are spastic motor deficits. Different pathogenetic mechanisms may underlie hypoxic-ischaemic injury of the brain such as decreased blood flow autoregulation, altered cerebral metabolism, thrombosis, haemorrhage, accumulation of toxic metabolites such as glutamate, impaired intracellular calcium turnover, release of interleukins and prostaglandins, iron accumulation and overproduction of free-radicals. In summary, hypoxia-ischaemia in neonates triggers a cascade of biological processes culminating in cell death. Important advances in the assessment of cerebral injuries in neonates have been made in the area of neuroimaging, especially in magnetic resonance imaging which may provide useful prognostic information when obtained in the course of brain injury. Future studies may focus on new therapeutic pharmacological and non-pharmacological strategies aimed at the reversal of the pathophysiological mechanisms activated by perinatal hypoxia-ischaemia.

Brain Damage, Chronic↗
PubMed2000

The prolonged duration of rocuronium in Chinese patients.

We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0. 12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T(1)) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T(1) 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P<0.05 for T(1) of 10%, 25%, 75%, and 90% and TOF to 0.7). The 50% effective dose was smaller in Chinese adults (125+/-63 vs. 159+/-66 microg/kg) and Chinese children (171+/-43 vs. 191+/-46 microg/kg) than in Caucasian adults and children, but the difference was not statistically significant. In adults, time to 25% T(1) recovery was 43+/-13 min in Chinese patients and 33+/-10 min in Caucasian patients (P<0.05). The corresponding values were more rapid for children: 30+/-10 and 24+/-6 min (P<0.05). We conclude that the recovery from rocuronium neuromuscular blockade was longer in Chinese compared with Caucasian patients and in adults compared with children.

Adolescent↗
PubMed2000

Temporal relation between acoustic and force responses at the adductor pollicis during nondepolarizing neuromuscular block.

BACKGROUND: Contracting muscle emits sounds. The purpose of this study was to compare the time course of muscular paralysis at the adductor pollicis muscle (AP) with use of acoustic myography and mechanomyography. METHODS: Thirteen elective surgery patients, American Society of Anesthesiologists physical status I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general anesthesia. Force of AP was measured with use of a strain gauge, and sounds were recorded simultaneously with use of a small condenser microphone fixed on the palmar surface of the hand over the AP. Supramaximal stimulation was applied to the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train-of-four stimulation was also recorded during recovery. RESULTS: Force and sounds both were equally sensitive in measuring maximum block. The relation between sound and force was curvilinear, with good agreement near 0 and 100% and acoustic response exceeding mechanical response at intermediate levels of block. The acoustic signal had a slower onset and a faster recovery than the force response. The fade response of sound to train-of-four stimulation also recovered faster than that of force. CONCLUSION: Acoustic myography is an alternative method to monitor muscular paralysis that is easy to set up and applicable to most superficial muscles. However, the time course of relaxation at AP using acoustic myography differs from the time course of force relaxation. Therefore, these two methods are not equivalent when applied to AP.

Adult↗