Assessment of co-ingestion effects on poisoning patterns, drug-drug interactions, and adverse outcomes in acute toxic exposure.

ABSTRACT

Multiple toxic exposures are increasing nowadays. In cases of acute poisoning involving multiple agents, there is a potential for additional toxicity that goes beyond the effects and toxicity of each drug. Very scarce studies have investigated the problem of multiple toxic exposures where the information on drug-drug interactions (DDIs) originates from clinical experience, which is inconclusive and cannot be generalized to patients. Therefore, the current study aimed to explore the influence of co-ingestion on the clinical presentation of exposed patients and to identify the common associated DDIs and their effect on poisoning outcomes, including the need for mechanical ventilation (MV), intensive care unit (ICU) utilization, and prolonged hospital stay. The current study is a retrospective cross-sectional study that was conducted using medical records of 169 adult patients admitted to a poison control center and diagnosed with acute drug poisoning. Of them, 40.8 % were exposed to multiple drugs. The total number of drugs reported in the current study was 320 preparations, with an average of 1.9 drugs per patient. There were about 726 potential DDIs; more than half of these interactions were significant (n = 486). Antidepressants and psychotropics showed the highest total number of DDIs. Patients with multiple ingestion were significantly older and this pattern of exposure was more frequent among suicidal attempters, substance abusers, cardiac patients, and patients diagnosed with neurological and psychological problems. Moreover, patients with multiple ingestions showed severe presentations indicated by higher grades of Poison Severity Score and lower Glasgow Coma Scale. Multiple ingestion was associated with higher liability for MV, ICU admission, and prolonged length of hospital stay (p < 0.001). There was a significant moderate direct correlation between the number of drugs consumed and the number of resulting DDIs (r = 0.542, p < 0.001). There was a significant direct correlation between the occurrence of significant chronic/chronic drug interactions from one side and the history of substance abuse (r = 0.596, p = 0.041) and psychological illness (r = 0.662, p = 0.019) from the other side. Moreover, significant acute/acute drug interactions were correlated with being male (r = 0.969, p < 0.001) of older age (r = 0.672, p = 0.024). Similarly, significant acute/chronic drug interactions were moderately correlated with being a male (r = 0.692, p = 0.013). The presence of epilepsy and psychological problems were the main significant predictors of multiple acute toxic exposures. Among the patients exposed acutely to more than one agent who were on long-term treatment, exposure to three drugs or more could significantly predict the need for MV with excellent area under the curve (AUC) of 0.896 and 77.0 % accuracy. Moreover, and it was a fair predictor of ICU admission (AUC = 0.625), with an 88.9 % ability to exclude patients unlikely to need ICU admission. Particular attention should be paid to the patients at risk of potential DDIs. When prescribing drugs, the minimum number of drugs with the lowest effective doses, and minimal potential DDIs should be prioritized.