THe characteristics and costs of severe theophylline toxicity in a tertiary critical care unit in Eastern Cape Province, South Africa

Severe theophylline toxicity requiring haemodialysis accounts for approximately one-third of drug toxicity cases admitted to the Livingstone Tertiary Hospital (LTH) intensive care unit (ICU) in Gqeberha, South Africa, imposing a significant resource burden.Objectives. To investigate the characteristics and burden of severe theophylline toxicity in an Eastern Cape Province tertiary hospital adult ICU.Methods. A retrospective review of all severe theophylline toxicity admissions to the ICU from 1 January 2013 to 31 December 2018 was conducted. Demographic and clinical data were captured and analysed. The National Department of Health 2019 fees schedule was used to calculate costs based on duration of ICU stay and number of haemodialysis sessions received.Results. Of the 57 patients included in the study, 84% were cases of deliberate self-harm. The majority were aged <40 years (77%) and female (79%). The mean (standard deviation (SD)) initial serum theophylline level was 612 (269) µmol/L. Complications included convulsions (n=12; 21%), arrhythmias (n=9; 16%), need for mechanical ventilation (n=7; 12%) and death (n=4; 7%). The main risk factors for these complications were age ≥30 years, an inappropriately normal or elevated initial serum potassium level, an elevated serum creatinine kinase level and an elevated initial serum theophylline level. Receiver operator characteristic curve analysis assessing the initial serum theophylline level as a discriminator for life-threatening complications produced an area under the curve of 0.71 for serum theophylline >400 µmol/L (sensitivity 88%, specificity 12%). All the 4 patients who died had an initial serum theophylline level >1 000 µmol/L. The mean (SD) cost per admission amounted to ZAR16 897 (10 718), with a mean of one 4-hour dialysis session per admission.Conclusion. Severe theophylline toxicity, usually in the context of deliberate self-harm, is a preventable yet life-threatening toxicity encountered at LTH. Demographic risk factors include young females from certain areas in and around Gqeberha. Risk factors for complications include older age, paradoxically normal or elevated serum potassium levels, elevated serum creatinine kinase levels and an initial serum theophylline level >400 µmol/L. Patients with these clinical features should be closely monitored and treated timeously at an appropriate level of care. The need for ICU admission and dialysis, both limited resources, makes the treatment of severe theophylline toxicity costly. Further studies of the underlying psychosocial drivers, local prescribing practices and preventive interventions related to severe theophylline toxicity are required.

Emergence of T-lymphocytes, eosinophils and dendritic cells in the bronchi of actively sensitized guinea pigs after antigenic challenge

Bronchi from guinea pigs actively sensitized to ovalbumin and boosted two weeks later display increased numbers of CD4+ T-lymphocytes and eosinophils. We have further investigated immunopathological changes in sensitized guinea pigs 2 or 24 h after antigenic challenge with ovalbumin. Lungs were resected, frozen and cryostat sections stained with monoclonal antibodies that recognize relevant guinea pig epitopes. Cyanide-resistant peroxidase activity was used to stain eosinophils. No further increase in T-lymphocytes or eosinophils was observed 2 h after challenge. At 24 h, a marked increase in EPO+ eosinophils was found, and this was accompanied by severe mucosal damage characterized by epithelial shedding and ulceration. The numbers of T-lymphocytes remained stable but a novel population of cells with the appearance of dendritic cells was seen in the bronchial wall. They were negative for macrophage markers but were strongly Class II positive. These findings suggest that antigenic challenge results in further recruitment of eosinophils, their activation and release of toxic substances to the epithelium. Furthermore, other cell types, possibly dendritic cells, are attracted to the bronchi and could play a role in maintaining allergic inflammation via antigen presentation.