Sharif Asmaa Fady, Alshammari Rayan Yousef, Alghamdi Fawaz Talaat, Almutairi Sultan Ahmed, AlGhamdi Abdullah Saeed, Al-Nazhan Abdulaziz Saad, AlNasser Shahd, Al-Mulhim Khalid A
Department of Clinical Medical Sciences, College of Medicine, Dar AL-Uloom University, Al Falah, Riyadh 13314, Kingdom of Saudi Arabia.
Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, El Bahr St., Tanta, Gharbia Governorate 31111, Egypt.
Toxicol Rep. 2024 Aug 8;13:101705. doi: 10.1016/j.toxrep.2024.101705. eCollection 2024 Dec.
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.
如今,多种毒物暴露的情况日益增多。在涉及多种药物的急性中毒病例中,可能存在超出每种药物单独作用和毒性的额外毒性。极少有研究探讨多种毒物暴露问题,其中关于药物相互作用(DDIs)的信息来源于临床经验,而这些经验尚无定论,也无法推广至所有患者。因此,本研究旨在探讨同时摄入多种药物对暴露患者临床表现的影响,识别常见的相关药物相互作用及其对中毒结局的影响,包括机械通气(MV)需求、重症监护病房(ICU)使用情况以及住院时间延长。本研究是一项回顾性横断面研究,使用了169例入住中毒控制中心并被诊断为急性药物中毒的成年患者的病历。其中,40.8%的患者暴露于多种药物。本研究中报告的药物总数为320种制剂,平均每位患者1.9种药物。存在约726种潜在的药物相互作用;其中一半以上的相互作用具有显著性(n = 486)。抗抑郁药和精神药物显示出的药物相互作用总数最多。同时摄入多种药物的患者年龄显著更大,这种暴露模式在自杀未遂者、药物滥用者、心脏病患者以及被诊断患有神经和心理问题的患者中更为常见。此外,同时摄入多种药物的患者表现出严重症状,表现为中毒严重程度评分较高和格拉斯哥昏迷量表得分较低。同时摄入多种药物与机械通气、入住ICU以及住院时间延长的更高可能性相关(p < 0.001)。所摄入药物数量与产生的药物相互作用数量之间存在显著的中度正相关(r = 0.542,p < 0.001)。一方面,显著的慢性/慢性药物相互作用的发生与药物滥用史(r = 0.596,p = 0.041)和心理疾病(r = 0.662,p = 0.019)另一方面存在显著的正相关。此外,显著的急性/急性药物相互作用与男性(r = 0.969,p < 0.001)和年龄较大(r = 0.672,p = 0.024)相关。同样,显著的急性/慢性药物相互作用与男性(r = 0.692,p = 0.013)呈中度相关。癫痫和心理问题的存在是多种急性毒物暴露的主要显著预测因素。在长期接受治疗且急性暴露于不止一种药物的患者中,暴露于三种或更多药物可显著预测机械通气需求曲线下面积(AUC)为0.896,准确率为77.0%。此外,它是入住ICU的良好预测指标(AUC = 0.625),有88.9%的能力排除不太可能需要入住ICU的患者。应特别关注有潜在药物相互作用风险的患者。开药时,应优先选择有效剂量最低、潜在药物相互作用最少的最少数量药物。