摘要:

Awareness during general anaesthesia is still a remarkable problem in modern anaesthetic practice. Fortunately, the incidence of awareness with explicit recall of severe pain is low, with a frequency of fewer than 1 event in 3000 anaesthetic episodes. For modern routine anaesthesia the incidence of explicit recall of intraoperative perception is only slightly higher, at about 1 event in 1000 procedures. General anaesthesia for caesarean section, cardiac operations, acute trauma management or bronchoscopy seems to carry a higher risk of intraoperative awareness. The incidence of subconscious awareness with implicit recall of auditory perception, and of amnesic but conscious awareness, is methodologically very hard to assess but can be as high as 100%, depending on the anaesthetic regimen used.The highest incidence of intraoperative awareness is associated with the use of specifically acting, mostly receptor-mediated drugs, such as opioids, benzodiazepines or the weak anaesthetic nitrous oxide, given alone or in combination. In contrast, volatile anaesthetics such as halothane, enflurane, isoflurane, sevoflurane and desflurane, as well as potent intravenous anaesthetics such as methohexital, thiopental, etomidate and propofol in appropriate concentrations, successfully block any intraoperative perceptions. Volatile anaesthetics offer the advantage that the concentration of the drug is easily controlled by monitoring end-expiratory gas concentrations. On the other hand, sophisticated dosage strategies for the use of intravenous agents, for example propofol and alfentanil, offer the chance to achieve an incidence of awareness during total intravenous anaesthesia as low as that seen for volatile anaesthetics.Constant attention to the possibility of awareness, along with an appropriate monitoring of the depth of the anaesthesia, helps to avoid awareness. Although observing clinical signs is the most common method, it is a very poor indicator for intraoperative awareness. Electrophysiological measurements can help to guide the anaesthesiologist's decisions. Derived parameters of the raw electroencephalogram, such as the spectral edge frequency, may help to assess relevant individual pharmacokinetic or pharmacodynamic properties for the anaesthetics used. Midlatency auditory evoked potentials seem to be a promising measure for assessing depth of anaesthesia, although further studies are needed to confirm their clinical usefulness.Any instance of intraoperative awareness should be treated sympathetically and seriously by the responsible anaesthesiologist. Aid should be provided to the patients to minimise long lasting psychological sequelae. In the worst case a post-traumatic stress disorder syndrome may develop, requiring intensive psychological or even psychiatric treatment for the patient.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Depression is present in about 40% of patients with dementia. Whereas most studies of depression in dementia are carried out in patients with Alzheimer's dementia, depression is also a frequent finding in other types of dementia, such as ischaemic vascular dementia, dementia with Lewy bodies and fronto-temporal dementia. Longitudinal studies have demonstrated that untreated major depressions may last for more than 1 year in patients with dementia, whereas minor depression is of shorter duration. Despite the high incidence of depression in patients with dementia, few controlled studies have examined the usefulness of antidepressant drugs. Tricyclic antidepressants (TCAs) such as imipramine and clomipramine may be effective, but a high incidence of adverse effects such as orthostatic hypotension and urinary retention may limit their use to the subgroup of patients in whom tolerability is acceptable. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) such as citalopram and fluoxetine have efficacy similar to that of TCAs, but the incidence of adverse effects is substantially lower. Monoamine oxidase inhibitors have rarely been assessed in patients with dementia, although moclobemide has demonstrated good efficacy and tolerability in a single study. Although antidepressant drugs usually demonstrated greater efficacy than placebo, these differences were mostly slight and require further evaluation.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Epilepsy is a chronic disorder that requires adherence to long term anticonvulsant drug therapy for successful outcomes. Most established anticonvulsants must be taken several times a day because of short half-lives and narrow therapeutic indices. Extended release (ER) formulations of some anticonvulsants have been developed to reduce dose frequency and to maintain constant plasma drug concentrations, and to reduce adverse effects.For a drug to be a suitable candidate for ER formulation it must possess the following characteristics: a short half-life, no first-pass metabolism, a narrow therapeutic index, and efficient absorption throughout the gastrointestinal tract. Of the currently available anticonvulsants, carbamazepine and valproic acid (sodium valproate) are the most suitable candidates for ER formulation.Several carbamazepine ER formulations have been developed. These formulations include Carbatrol®, Tegretol-XR®, Tegretol Retard®, Neurotol Slow®, Trimonil Retard®and Teril CR®, among others. Valproic acid ER formulations have also been developed. Although there are currently no ER formulations of valproic acid marketed in the US, several are available in Europe including Epilim Chrono®and Depakine Chrono®. The Depakote Sprinkle®formulation is also available in some European countries.Of the newer anticonvulsants tiagabine is the most likely candidate for future ER formulation.ER formulations offer the advantage of better patient compliance due to decreased frequency of administration and adverse effects. Also, less fluctuation in plasma concentrations makes monitoring of drug concentrations more viable. These advantages should lead to better seizure control and improve quality of life for the patient.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

There is increasing evidence that inflammatory processes play a central role in atherosclerosis and in secondary infarct growth after focal cerebral ischaemia. Focal cerebral ischaemia is often the result of arterio-arterial thromboembolism arising from plaques in the internal carotid artery (ICA). In the ICA, the extent of inflammatory infiltration by T cells and macrophages, and the expression of matrix metalloproteinase-9 in high grade stenoses, correlate with clinical features of plaque destabilisation.Within the CNS, focal ischaemia induces a strong inflammatory response, with recruitment of granulocytes, T cells and macrophages which is facilitated by early upregulation of cell adhesion molecules. In experimental animals, anti-adhesion strategies have led to a dramatic reduction of stroke volumes; however, these strategies have failed to be effective in humans.‘Immunological’ transcription factors and inducible nitric oxide synthase are upregulated in focal ischaemia and contribute to secondary infarct growth between 24 and 72 hours after the initial insult. The cytokines interleukin-1β and tumour necrosis factor-α are induced prior to inflammation. Functionally, these cytokines exert both neurotoxic and neuroprotective effects after cerebral ischaemia.At present, immunological strategies targeted at a single immunomodulator for the treatment of stroke are hampered by an incomplete understanding of the complex cellular and molecular interactions that lead to divergent functional effects of inflammatory cells and immunological mediators after focal ischaemia.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Since December 1999, 3 drugs have been cleared for marketing by the US Food and Drug Administration for the treatment of partial-onset seizures in adults with epilepsy − levetiracetam, oxcarbazepine and zonisamide. All are approved as adjunctive therapy; oxcarbazepine is also approved as monotherapy. Levetiracetam appears to have a novel mechanism of action, while the others block voltage-sensitive sodium channels (oxcarbazepine and zonisamide) and T-type calcium channels (zonisamide). Levetiracetam and oxcarbazepine have short serum elimination half-lives and can be started at therapeutic dosages. All 3 drugs exhibit linear pharmacokinetics and have a low propensity for drug-drug interactions. There is extensive worldwide experience with oxcarbazepine and zonisamide, whereas exposure to levetiracetam has been limited to a relatively small number of patients in clinical trials.These 3 drugs are important additions to the armamentarium for the treatment of seizures and offer patients whose lives are compromised by epilepsy the potential to achieve a better quality of life.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS