Lack of effect of theophylline on the outcome of acute cerebral infarction

Abstract

In patients with acute ischemic stroke, dramatic but often transient improvements have been noticed after theophylline injections. Whether better results could be obtained by continuous infusion of the drug was evaluated in a double-blind study. Out of 46 patients with a mean age of 75 years, 22 got theophylline as aminophylline (bolus dose of 230 mg followed by 0.5 mg/kg/h) and 24 placebo during 3 days. The groups were comparable in all aspects at the outset of the trial. Serum theophylline concentrations were kept within the therapeutic range recommended for patients with asthma. No significant difference in outcome was noticed between the groups during the hospital period when repeated neurological assessments by two different scores and mortality were compared.

Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke

“…For the placebo group one trial used physiological saline (Geismar 1976) and the other used 5.5% glucose (Britton 1980). Aminophylline was administered as either a 200 mg intravenous bolus dose (10 ml 2% solution in saline) infused over two minutes followed by 10 ml at three hours and 10 ml at six hours (Geismar 1976), or by intravenous loading dose of 230 mg followed by continuous intravenous infusion (0.5 mg/kg/h in 5.5% glucose) for 72 hours (Britton 1980). One trial reported change in neurological impairment using a locally developed scoring system (Geismar 1976); this trial also reported the Rankin score at three weeks.…”

“…One trial reported change in neurological impairment using a locally developed scoring system (Geismar 1976); this trial also reported the Rankin score at three weeks. The other trial reported changes in functional capacity, based on the patients ability to walk (Britton 1980). None of the trials reported quality of life.…”

“…One trial randomised patients by sealed numbered envelopes (Britton 1980); the other trial was randomised by coded numbered boxes (ampoules) supplied by the hospital pharmacist (Geismar 1976). None of the studies explicitly stated that they were analysed by intention-to-treat, however, it is clear in one trial (Britton 1980) that no patients were lost to follow up; six patients were lost to follow up in the trial of Geismar (Geismar 1976), three in the treatment group and three in the control group. Both trials were single centre and involved 79 (Geismar 1976) and 46 (Britton 1980) patients respectively.…”

“…None of the studies explicitly stated that they were analysed by intention-to-treat, however, it is clear in one trial (Britton 1980) that no patients were lost to follow up; six patients were lost to follow up in the trial of Geismar (Geismar 1976), three in the treatment group and three in the control group. Both trials were single centre and involved 79 (Geismar 1976) and 46 (Britton 1980) patients respectively. One trial used lumbar puncture CSF analysis in two-thirds of the patients to exclude cerebral haemorrhage (Geismar 1976), the other used lumbar puncture or brain scintography (Britton 1980).…”

Neuroprotection in acute ischaemic stroke. II: Clinical potential

“…However, two small trials have provided little indication of any long-term benefits from aminophylline infusion during the acute stages. 87,88 Blood pressure augmentation with plasma expanders and inotropic agents is now an established part of the management of focal cerebral ischaemia following subarachnoid haemorrhage, and experimental results suggest that it has considerable promise as a therapeutic intervention in acute Vascular Medicine 1999; 4: 149-163 stroke. 89,90 As yet there are few reliable clinical studies on the use of inotropic or vasopressor drugs in stroke, but haemodilution using volume expanders alone, with or without venesection, has been quite widely evaluated, both experimentally and clinically.…”