[Do anesthetics impair brain development?].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E Tassonyi.
Explore the source record for details and available documents.
The bispectral index (BIS) was used to examine the hypnotic efficacy of propofol in 25 smokers (20 cigarettes/day for 2 years) and 24 matched non-smokers (same gender, age, height, weight). BIS was recorded at baseline, at four incremental effect-site concentrations of propofol and at loss of consciousness. Compared with non-smokers, smokers were found to have higher BIS values at baseline (mean (SD)) (97 (1) vs 98 (1)), at 0.7 microg x ml(-1) (95 (3) vs 97 (1)) and at 1.1 microg x ml(-1) (89 (6) vs 94 (4)), p = 0.0099, and they lost consciousness at higher propofol concentrations (2.0 (0.4) vs 2.4 (0.8) microg x ml(-1)), p = 0.03, and at lower BIS values (66 (10) vs 60 (10)), p = 0.04. The hypnotic efficacy of propofol is reduced when used at low effect-site concentrations in smokers. This phenomenon may have some impact on the management of smokers undergoing sedation using target controlled infusion systems.
BACKGROUND: The induction characteristics of propofol 1% and 2% were compared in children undergoing ENT surgery, in a prospective, randomized, double-blind study. METHODS: One hundred and eight children received propofol 1% (n=55) or 2% (n=53) for induction and maintenance of anaesthesia. For induction, propofol 4 mg kg(-1) was injected at a constant rate (1200 ml h(-1)), supplemented with alfentanil. Intubating conditions without the use of a neuromuscular blocking agent were scored. RESULTS: Pain on injection occurred in 9% and 21% of patients after propofol 1% and 2%, respectively (P=0.09). Loss of consciousness was more rapid with propofol 2% compared with propofol 1% (47 s vs 54 s; P=0.02). Spontaneous movements during induction occurred in 22% and 34% (P=0.18), and intubating conditions were satisfactory in 87% and 96% (P=0.19) of children receiving propofol 1% or 2%, respectively. There were no differences between the two groups in respect of haemodynamic changes or adverse events. CONCLUSIONS: For the end-points tested, propofol 1% and propofol 2% are similar for induction of anaesthesia in children undergoing minor ENT surgery.
BACKGROUND: Neuromuscular blocking agents may exert central nervous system effects when they reach the brain. This study assessed the concentrations and the time course of passage of vecuronium, atracurium, and its metabolite laudanosine in the cerebrospinal fluid (CSF) of patients undergoing intracranial aneurysm clipping. METHODS: Twenty-five patients with subarachnoid hemorrhage were randomly allocated to receive an intravenous infusion of vecuronium (n=13) or atracurium (n=12). Arterial blood and lumbar CSF were sampled before and 1, 2, 3, 4 and 8 h after the start of the relaxant infusion. The samples were analyzed by liquid chromatography-electrospray ionization mass spectrometry (vecuronium) and high-pressure liquid chromatography (atracurium and laudanosine). RESULTS: The data of 20 patients (10 in both groups) were analyzed. In 11 CSF samples from five patients atracurium was detected in concentrations from 10 to 50 ng/ml. Laudanosine was retrieved in all CSF samples at 1, 2, 3, 4 and 8 h; the highest CSF concentration of laudanosine occurred at 3 h [38 (18-63) ng/ml: median (range)]. Vecuronium was not found in any CSF sample. CONCLUSION: Significant concentrations of atracurium and laudanosine but not of vecuronium were detected in the CSF of patients during and immediately after intracranial aneurysm surgery.
The bispectral index (BIS) and a sedation score were used to determine and compare the effect of propofol in the presence of fentanyl, alfentanil, remifentanil and sufentanil. Seventy-five non-premedicated patients were assigned randomly into five groups (15 in each) to receive fentanyl, alfentanil, remifentanil, sufentanil or placebo. Opioids were administered using a target-con-trolled infusion device, to obtain the following predicted effect-site concentrations: fentanyl, 1.5 ng ml(-1); alfentanil, 100 ng ml(-1); remifentanil, 6 ng ml(-1); and sufentanil, 0.2 ng ml(-1). After this, a target-controlled infusion of propofol (Diprifusor) was started to increase concentration gradually, to achieve predicted effect-site concentrations of 1, 2, and 4 microg ml(-1). At baseline and at each successive target effect-site concentration of propofol, the BIS, sedation score and haemodynamic variables were recorded. At the moment of loss of consciousness (LOC), the BIS and the effect-site concentration of propofol were noted. The relationship between propofol effect-site concentration and BIS was preserved with or without opioids. In the presence of an opioid, LOC occurred at a lower effect-site concentration of propofol and at a higher BIS50 (i.e. the BIS value associated with 50% probability of LOC), compared with placebo. Although clinically the hypnotic effect of propofol is enhanced by analgesic concentrations of mu-agonist opioids, the BIS does not show this increased hypnotic effect.
BACKGROUND: Curaremimetic nondepolarizing muscle relaxants are widely used in clinical practice to prevent muscle contraction either during surgery or during intensive care. Although primarily acting at the neuromuscular junction, these compounds can cause adverse effects, including modification of cardiac rhythm, arterial blood pressure, and in the worst cases, triggering of seizures. In this study, we assessed the interaction of atracurium and its metabolite, laudanosine, with neuronal nicotinic receptors. METHODS: The human neuronal nicotinic receptors alpha4beta2, alpha3beta4, alpha3alpha5beta4, and alpha7 are heterologously expressed in Xenopus laevis oocytes, and the effect of atracurium and its degradation product, laudanosine, were studied on these receptors. RESULTS: Atracurium and laudanosine inhibited in the micromolar range the major brain alpha4beta2 receptor and the ganglionic alpha3beta4 or alpha3beta4alpha5 and the homomeric alpha7 receptors. For all four receptors, inhibition was rapid and readily reversible within less than 1 min. Atracurium blockade was competitive at alpha4beta2 and alpha7 receptors but displayed a noncompetitive blockade at the alpha3beta4 receptors. Inhibition at this receptor subtype was not modified by alpha5. Laudanosine was found to have a dual mode of action; first, it competes with acetylcholine and, second, it blocks the ionic pore by steric hindrance. At low concentrations, these two drugs are able to activate both the alpha4beta2 and the alpha3beta4 receptors. CONCLUSION: Adverse effects observed during atracurium administration may be attributed, at least partly, to an interaction with neuronal nicotinic receptors.
Explore the source record for details and available documents.
BACKGROUND: The present study compared the quality of neuromuscular block and costs after equipotent doses of mivacurium and vecuronium in the context of paediatric ENT surgery. METHODS: A total of 30 children undergoing elective tonsillectomy were included and randomised in two groups (n = 15 for each) according to the neuromuscular blocking agent (NMBA) used. Anaesthesia was induced with alfentanil (15 micrograms/kg), propofol (3 mg/kg) and either 0.2 mg/kg mivacurium or 0.14 mg/kg vecuronium. For maintenance of anaesthesia propofol (8-12 mg/kg/h) was given. Neuromuscular block was assessed by electromyography using train-of four stimulation and the following parameters were quantified: Twitch height (T1) 2 min after the initial bolus of the myorelaxant; duration until recovery to 10% T1, number and duration of bolus injections of the myorelaxant needed to maintain neuromuscular block to a T1 < 10%. In addition, the intubating conditions, number of patients needing pharmacological reversal at the end of surgery, adverse reactions and the costs for neuromuscular block and pharmacological antagonization were assessed. RESULTS: Intubation conditions were comparable between both study groups: mivacurium--excellent: 7, good: 5, not acceptable: 1; vecuronium--excellent: 11, good: 4 (n.s.). T1 at 2 min was 16 (15)% for mivacurium and 6 (9)% for vecuronium (P < 0.05). Time to 10% T1 recovery was 6.1 (1.7) min for mivacurium and 21.8 (3.7) min for vecuronium (P < 0.01). In the mivacurium group 7 repetitive doses (range: 4-18) were needed to maintain T1 < 10% during surgery, whereas children treated with vecuronium needed only 1 maintenance dose (range: 0-2) (P < 0.01). Two children in the mivacurium group and 11 in the vecuronium group required pharmacological reversal of the NMB at the end of surgery (P < 0.01). The overall costs of NMB were significantly higher in the mivacurium group as compared to vecuronium 12.88 (4.5) Euro vs 9.96 (2.4) Euro; P < 0.05. CONCLUSIONS: In conclusion, mivacurium-induced NMB is of very short duration in paediatric patients, and therefore repetitive doses are required to maintain a deep neuromuscular block. Nevertheless, residual paralysis is less frequent after mivacurium. The neuromuscular block after mivacurium was more expensive and residual paralysis less frequent compared to vecuronium.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Using rat hippocampal slices, we studied the effects of nicotine and three antagonists of neuronal nicotinic receptors on excitatory and inhibitory transmission. We report that nicotine at concentrations between 0.5 and 100 microM enhanced excitatory synaptic responses and increased the size of the presynaptic fiber volley. This effect was reproduced by three neuronal nicotinic receptor antagonists: dihydro-beta-erythroidine, methyllycaconitine and mecamylamine. In contrast, nicotine, but not nicotinic antagonists, produced a dual effect on inhibition: nicotine enhanced gamma-aminobutyric-acid A (GABA(A)) receptor-mediated synaptic responses at low concentration (0.5 microM) and blocked them at high concentration (100 microM). We conclude that the excitatory effects of nicotine are reproduced by nicotinic receptor antagonists, thereby suggesting that these effects might be mediated through receptor desensitization. These results also indicate that nicotine differentially affects GABAergic inhibition at low and high concentrations-effects that are not reproduced by antagonists.
We have investigated the dose-effect relationship of neostigmine in antagonizing vecuronium-induced neuromuscular block with and without magnesium sulphate (MgSO4) pretreatment. Neuromuscular block was assessed by electromyography with train-of-four (TOF) stimulation. First, we determined neostigmine-induced recovery in patients pretreated with MgSO4 (group A) or saline (group B) (n = 12 each). The height of T1, 5 min after neostigmine, was 43 (7)% in group A and 65 (6)% in group B (P < 0.01). Respective values after 10 min were 59 (7)% and 83 (5)% (P < 0.01). TOF ratio, 5 min after neostigmine, was 29 (6)% in group A and 29 (5)% in group B. Respective values after 10 min were 38 (11)% and 51 (7)% (P < 0.01). To gain insight into the mechanisms leading to delayed recovery after MgSO4, we calculated assisted recovery, defined as neostigmine-induced recovery minus mean spontaneous recovery. Spontaneous recovery was assessed in another 24 patients. Patients in group C received MgSO4/vecuronium and patients in group D vecuronium only (n = 12 each). Five minutes after neostigmine, assisted recovery was 22 (7)% in the MgSO4 pretreated patients and 28 (6)% in controls (P < 0.05). Ten minutes after neostigmine, values were 24 (7)% and 22 (6)%. Maximum assisted recovery was not influenced by MgSO4 pretreatment (27 (6)% in group A and 32 (6)% in group B) and time to maximum effect was comparable between groups: 6 (4-10) min and 7 (5-8) min, respectively. We conclude that neostigmine-induced recovery was attenuated in patients treated with MgSO4. This was mainly a result of slower spontaneous recovery and not decreased response to neostigmine.
Explore the source record for details and available documents.
BACKGROUND: Blood requirements for Head and Neck surgical procedures have not been studied carefully. In order to set up an autotransfusion program, the blood loss and transfusion requirements should be known precisely. METHODS: The blood bank database was used to determine which Head and Neck procedures required blood transfusion during the previous 5 years. A list of 10 transfusion-associated operations was established, the records of all patients who underwent these procedures during a 5-year period were reviewed, and average the blood loss and number of units transfused determined. RESULTS: All procedures were for cancer resection. The operations were classified in 3 groups according to their transfusion probability: high (> 80%), low (< 5%) and moderate. For the moderate transfusion group, age, preoperative hemoglobin, and past medical history of cardiac and pulmonary disease were associated with higher incidence of transfusion. An average delay of 3 weeks was found between the diagnosis and the actual surgery. CONCLUSION: The transfusion requirements of Head and Neck surgical procedures could be safely met by an autotransfusion protocol, given the average delay of 3 weeks between diagnosis and surgery.
We describe a 73-yr-old woman anaesthetized for a laminectomy. She suffered from hepatic failure with mild encephalopathy complicated by several exacerbations associated with sedative and opioid therapy. The challenge for anaesthesia management was to provide adequate analgesia and avoid causing hepatic encephalopathy during and after the surgery. We used remifentanil to provide intraoperative and postoperative analgesia, because it has a short duration of action and does not require hepatic metabolism. We closely monitored the respiratory and the neurological status throughout the administration and conclude that remifentanil can provide perioperative analgesia in patients at risk of developing hepatic encephalopathy.
UNLABELLED: Drugs interacting with opioid or N-methyl-D-aspartate (NMDA) receptors may have differing effects on post-surgical sensory changes, such as central inhibition or spinal excitation. We compared the effect of supplementing isoflurane/N2O/O2 anesthesia with an opioid agonist (fentanyl [n = 15]) or two drugs inhibiting the NMDA system differently (magnesium, ketamine [n = 15 in each group]) on sensory changes after abdominal hysterectomy. Electric sensation, pain detection, and pain tolerance thresholds were determined (preoperatively and 1, 4, 24 h, and 5 days postoperatively) in arm, thoracic, incision, and leg dermatomes together with pain scores and cumulative morphine consumption. Thresholds relative to the arm were derived to unmask segmental sensory changes hidden by generalized changes. Absolute thresholds were increased 1-24 h, returning to baseline on Day 5, without overall differences among drugs. Fentanyl thresholds were lower 1 h and higher 5 days postoperatively compared with magnesium and ketamine; thresholds were lower at 24 h for magnesium versus ketamine. Relative thresholds increased compared with baseline only with fentanyl (1-4 h); none decreased. Pain scores and morphine consumption were similar. Thus, all adjuvants suppressed spinal sensitization after surgery. Fentanyl showed the most, and magnesium the least, central sensory inhibition up to 5 days postoperatively, with different patterns of inhibition directly postsurgery versus later. Differences in sensory processing were not reflected in clinical measures. IMPLICATIONS: We studied the effects on postsurgical sensory processing of general anesthesia supplemented by drugs affecting opioid or N-methyl-D-aspartate receptors using sensory thresholds. Generalized central sensory inhibition, differently affected by the drugs, predominated after surgery. All drugs suppressed spinal excitation. Clinical pain measures did not reflect sensory change.
BACKGROUND: Although neuromuscular blocking agents do not cross the blood-brain barrier, they may penetrate the central nervous system under particular circumstances and eventually cause neurotoxic consequences. METHODS: The effects of neuromuscular blocking agents on excitatory and inhibitory transmission in area CA1 of rat hippocampal slices were investigated using extracellular and intracellular recording techniques. RESULTS: Application of atracurium in the perfusion medium resulted in a dose-dependent enhancement of excitatory synaptic responses averaging 48.7 +/- 4.3% at a concentration of 10 nM. This effect was correlated with an increase in the size of the presynaptic fiber volley. Laudanosine, but not pancuronium bromide or vecuronium bromide, produced similar changes. In addition, atracurium and laudanosine blocked inhibitory transmission and reduced intracellularly recorded gamma-aminobutyric acidA receptor-mediated potentials. These effects were observed only at concentrations >1 microM and were not reproduced by pancuronium bromide and vecuronium bromide. CONCLUSIONS: Atracurium and its metabolite, laudanosine, contrary to pancuronium bromide and vecuronium bromide, produce two distinct effects on hippocampal slices. They enhance excitatory transmission and neuronal excitability and they block inhibitory gamma-aminobutyric acidA-mediated synaptic responses.