Experience with Althesin in the management of persistently raised ICP following severe head injury.

Of 243 patients who underwent intracranial pressure (ICP) monitoring after severe head injury, 42 (17%) were found to have severe persistently raised ICP, in spite of hyperventilation, mannitol, and surgical decompression. Althesin was infused to reduce ICP in these patients. This agent was shown to be effective and safe in reducing ICP, and a significant improvement in cerebral perfusion pressure was demonstrated. In this respect, Althesin may be more effective than barbiturates. However, no improvement in patient outcome was demonstrated in this series.

In vivo interactions between the benzodiazepine antagonist Ro 15-1788 and the steroid anaesthetic althesin in rats.

Althesin and delta 16-alphaxalone have been used alone and in combination with the benzodiazepine antagonist Ro 15-1788 to investigate any protective effect these drugs might have against bicuculline-induced convulsions in rats. We found that Althesin provided good protection against bicuculline-induced convulsions which was enhanced when Ro 15-1788 was also present. delta 16-Alphaxalone lacks the anaesthetic properties of Althesin, but did have some activity in preventing bicuculline-induced convulsions, although it was less effective than Althesin. Its action was not enhanced by treatment with Ro 15-1788. Although we have no definitive explanation of these results, it is possible that when Ro 15-1788 is used clinically, it may interact with other drugs not related chemically to the benzodiazepines.

Comparison of etomidate and althesin in the reduction of increased intracranial pressure after head injury.

The increasing use of shorter-acting hypnotic agents to control intracranial pressure (ICP) following severe head injury has prompted a prospective double-blind controlled trial comparing the efficacy of etomidate and Althesin, given by i.v. infusion. Over the dose ranges used, the two drugs appeared equipotent in decreasing ICP whilst preserving cerebral perfusion pressure. However, in two patients (one in each group) ICP did not respond to hypnotic infusion, a feature noted in other studies to occur in a minority of patients. With the cessation of Althesin manufacture and the discussion about the use of etomidate infusions, it is timely to document the effectiveness of etomidate in decreasing ICP.

Effect of long-term continuous infusion of alfathesin on clinical biochemical and haematological parameters.

Clinical biochemical and haematological parameters during long-term continuous infusion of alfathesin were studied in twelve neurosurgical patients who did not have multiple organ failure. Significant changes which were possibly caused by alfathesin were an alteration of blood film morphology, an elevation of plasma triglyceride and a reduction in plasma high-density lipids.

[Post-traumatic cerebral edema. Physiopathology and treatment]. / L'cedème cérébral post-traumatique. Physiopathologie et thérapeutique.

Severe head injury often produces complex intracranial displacements of the brain, resulting in widespread, often microscopic lesions. These are responsible for two types of edema: vasogenic edema, with outflow of molecules and fluid into the extracellular spaces by rupture of the blood-brain barrier and vasoplegia, and cytotoxic edema, with swelling of astrocytes due to membrane lesions. The connexions between these two types of edema are still obscure. Alterations in membrane phospholipids may impede function of Na-K pump enzymes, causing accumulation of water in the cell. Cerebral edema is responsible for intracranial hypertension and tentorial herniation, which in turn increase edema through venous compression, ischemia, and hypoxia. The least controversial anti-edema therapeutic measures include relative fluid and salt restriction, mannitol if called for, neuroplegia, in particular with diazepam and Gamma-OH, and assisted ventilation.

Althesin in the management of head injuries: a preliminary report.

The aggressive treatment of major craniocerebral trauma has received recent attention. Barbiturate administration has been beneficial in some cases of sustained, uncontrolled intracranial hypertension. One major disadvantage of pentobarbital narcosis is the long half-life of the drug (15 to 48 hours). We have used Althesin, an intravenous steroid anesthetic (alfaxalone and alfadolone acetate; Glaxo Laboratories Ltd., Greenford, Middlesex, England), in eight seriously head-injured patients. Althesin combines the theoretical advantages of pentobarbital in the management of head trauma with almost immediate reversibility (serum half-life, 1.6 minutes). Raised intracranial pressure and clinical outcome seem to be influenced favorably and the side effects are negligible when the drug is administered by continuous intravenous infusion over several days. Further study of this compound in the management of head trauma seems warranted.

Anticonvulsant activity of Althesin on experimental epilepsy.

Anaesthetic doses of Althesin were tested in rabbits using two experimental models of epilepsy: generalized (OHP; oxygen at high pressure-induced seizure) and partial (penicillin cortical-induced seizure). Althesin in both models always produced anticonvulsant activity which was more powerful in generalized convulsions. This agent was successful in preventing and treating OHP seizures. The authors conclude that a clinical history of convulsions must not be considered a contraindication to the use of this anaesthetic which has particularly useful properties for neurosurgery.

[Correlations between E.E.G. findings and intracranial pressure (ICP) during treatment of acute post-traumatic intracranial hypertension (preliminary report) (author's transl)]. / Corrélations E.E.g. - pression intra-cranienne au cours du traitement de l'hypergension intra-cranienne traumatoque aiguë par alfathésine (Note préliminaire).

An infusion of a 10% solution of Althesin was administered for treatment of acute post-traumatic intracranial hypertension. Six comatose patients, aged from 7 to 22 years, without neurosurgical lesions, were treated with doses of the compound varying from 40 to 400 ml per day for 1 to 6 days. Daily polygrahic recordings (E.E.G, E.M.G., E.K.G., respiration and I.C.P.) were made in all patients for periods of 4 to 8 hours. Doses lower than 0.12 ml/min. caused a slight reduction in I.C.P. in two patients, without variations in the E.E.G. Doses between 0.12 and 0.36 ml/min. provoked a reduction in I.C.P. in all patients, and the appearance of burst suppression in the E.E.G. in those patients with an "alternating" tracing only. Higher doses (0.36 to 0.72 ml/min.) caused a reduction in I.C.P. less than 50% in 5 of the 6 patients. Continuous slow wave tracings and border-line tracings showed less constant modifications. The reactivity of the I.C.P. and the E.E.G. to Althesin appears earlier and is more evident in patients with an alternating E.E.G. tracing and with pressure waves of the Lundberg type b. No side effects related to the use of barbiturates were noted after interrupting treatment.

Effects of althesin in psychotherapy of schizophrenics. Preliminary report.

Althesin infusions in subhypnotic dosage were given as a possible supportive agent during psychotherapy sessions in 6 chronic schizophrenics nonresponsive to neuroleptics and hardly amenable to psychotherapy. Speech content analysis (Gottschalk-Gleser method) of the therapy sessions of 2 patients gave the impression that there was lower hostility during Althesin sessions whereas anxiety was less influenced. The scoring from 2 patients in a self-rating scale on the state of wellbeing supported in impression of a beneficial effect of Althesin. Negative feelings were decreased and patients appeared to be more assertive.

[Althesin in the treatment of status epilepticus]. / L'althesin nel trattamento dello stato di male epilettico.

In view of its anticonvulsant effects in the experimental animal, its low toxicity, and its manageability, Althesin was used at doses of 80-600 mg in the treatment of barbiturate and benzodiazepine resistant epilepsy in 11 patients aged 15 months to 62 yr. Lasting suspension of the disease was obtained in 8 subjects. Burst suppression was achieved in 7 of these cases with 80-120 drops/min of a 10% solution of Althesin in 10% laevulose. No side-effects were observed.

The use of anesthetic drugs to reduce ICP changes in head-injured patients.

Chest physiotherapy causes increases in intracranial pressure (ICP) in patients with severe head injuries. In mechanically hyperventilated severe head injuries (PaCO2 3.3 - 4 kPa) 50% nitrous oxide in 50% oxygen exacerbated ICP increases associated with chest physiotherapy, while thiopentone and Althesin reduced these changes in ICP.

[Neuroanesthesiology in the child weighing less than 10 kilos: use of Alfatesine combined with a morphinomimetic]. / Neuroanesthésilogie chez l'enfant de moins de dix kilos: intérêts de l'Alfatésine associée a un morphinomimétique.

On the basis of the analysis of fifteen cases of children weighing less than ten kg, in a department of neurosurgery, the authors describe the use of Alfatésine by infusion in association with a morphinomimetic, a technique compatible with the existence of raised intracranial pressure. In view of the weight of the children, availability of a venous line represents a handicap and a danger to such an extent that the authors suggest limited assistance in the form of sedation by a halogenated agent, with the application of strict rules concerning dose and surveillance, bearing in mind its effects on intracranial pressure. The quality of anesthesia and of recovery is emphasised and the doses described. The effects of Alfatesine and of Fentanyl on intracranial pressure, cerebral metabolism and blood flow are reviewed. These favourable effects justify the use of Alfatesine in this context. One case of obvious overdose, responsible for delayed recovery, is discussed.