Clinical Pharmacy, Institute of Pharmacy, Medical Faculty, Leipzig University, and Drug Safety Center, Leipzig University and Leipzig University Hospital, Leipzig, Germany.
Division of Neuropediatrics, University Hospital for Children and Adolescents, Greifswald, Germany.
Paediatr Drugs. 2024 Sep;26(5):619-629. doi: 10.1007/s40272-024-00641-x. Epub 2024 Jul 4.
Children treated in a pediatric intensive care unit (PICU) often receive several drugs together, among them drugs defined as high-alert medications (HAMs). Those drugs carry a high risk of causing patient harm, for example, due to a higher potential for interactions. HAMs should therefore be administered with caution, especially in a PICU.
The objective of the current study was to identify drug-drug interactions involving HAMs that increase the risk of interaction-associated symptoms in pediatric intensive care.
In a retrospective study, we analyzed the electronic documentation of patients hospitalized for at least 48 h in a general PICU who received at least two different drugs within a 24-h interval. We assessed potential drug-drug interactions involving HAM on the basis of the two drug information databases UpToDate and drugs.com. Furthermore, we analyzed whether symptoms were observed after the administration of drug pairs that could lead to interaction-associated symptoms. For drug pairs involving HAM administered on at least 2% of patient days, and symptoms observed at least ten times after a respective drug pair, we calculated odds ratios, 95% confidence intervals, and p-values by using a univariate binary logistic regression.
Among 315 analyzed patients, 81.3% (256/315) received drugs defined as high-alert medication for pediatric patients. Those high-alert medications were involved in 20,150 potential drug-drug interactions. In 14.0% (2830/20,150) of these, one or more symptoms were observed that could be a possible consequence of the interaction, resulting in 3203 observed symptoms affecting 56.3% (144/256) of patients receiving high-alert medication. The odds ratios for symptoms observed after a drug-drug interaction were increased for eight specific symptoms (each p ≤ 0.05), especially hemodynamic alterations and disturbances of electrolyte and fluid balance. The odds ratio was highest for decreased blood pressure observed after the administration of the drug pair fentanyl and furosemide (OR 5.06; 95% confidence interval 3.5-7.4; p < 0.001). Increased odds ratios for specific symptoms observed after drug-drug interactions resulted from eight combinations composed of eight different drugs: digoxin, fentanyl, midazolam, phenobarbital, potassium salts and vancomycin (high-alert medications), and the diuretics furosemide and hydrochlorothiazide (non-high-alert medications). The resulting drug pairs were: potassium salts-furosemide, fentanyl-furosemide, vancomycin-furosemide, digoxin-furosemide, digoxin-hydrochlorothiazide, fentanyl-phenobarbital, potassium salts-hydrochlorothiazide, and midazolam-hydrochlorothiazide.
In a cohort of PICU patients, this study identified eight specific drug pairs involving high-alert medications that may increase the risk of interaction-associated symptoms, mainly hemodynamic alterations and electrolyte/fluid balance disturbances. If the administration of those drug pairs is unavoidable, patients should be closely monitored.
在儿科重症监护病房（PICU）接受治疗的儿童通常会同时接受多种药物治疗，其中包括被定义为高警示药物（HAM）的药物。这些药物有很高的导致患者伤害的风险，例如，由于更高的相互作用潜力。因此，HAM 应谨慎给药，尤其是在 PICU 中。
本研究的目的是确定涉及 HAM 的药物-药物相互作用，这些相互作用会增加儿科重症监护中与相互作用相关的症状的风险。
在一项回顾性研究中，我们分析了至少在普通 PICU 住院 48 小时以上且在 24 小时内接受至少两种不同药物的患者的电子病历。我们根据 UpToDate 和 drugs.com 这两个药物信息数据库评估了涉及 HAM 的潜在药物-药物相互作用。此外，我们还分析了在给予可能导致与相互作用相关的症状的药物对后是否观察到症状。对于至少有 2%的患者天数使用 HAM 给予的药物对，并且在各自的药物对之后观察到至少 10 次症状，我们通过使用单变量二项逻辑回归计算了比值比（OR）、95%置信区间（CI）和 p 值。
在 315 名分析的患者中，81.3%（256/315）接受了儿科患者定义为高警示药物的药物。这些高警示药物涉及 20,150 种潜在的药物-药物相互作用。在这些药物相互作用的 14.0%（2830/20,150）中，观察到一种或多种可能是相互作用后果的症状，导致 3203 种观察到的症状影响到 56.3%（144/256）接受高警示药物的患者。观察到药物-药物相互作用后出现症状的 OR 对于八个特定症状增加（每项 p≤0.05），尤其是血流动力学改变和电解质及液体平衡紊乱。在给予药物对芬太尼和呋塞米后观察到血压下降的 OR 最高（5.06；95%置信区间 3.5-7.4；p<0.001）。在药物-药物相互作用后观察到的特定症状的增加 OR 是由八种不同药物组成的八种组合引起的：地高辛、芬太尼、咪达唑仑、苯巴比妥、钾盐和万古霉素（高警示药物），以及利尿剂呋塞米和氢氯噻嗪（非高警示药物）。由此产生的药物对是：钾盐-呋塞米、芬太尼-呋塞米、万古霉素-呋塞米、地高辛-呋塞米、地高辛-氢氯噻嗪、芬太尼-苯巴比妥、钾盐-氢氯噻嗪和咪达唑仑-氢氯噻嗪。
在 PICU 患者队列中，本研究确定了八种可能增加与相互作用相关的症状风险的特定药物对，主要是血流动力学改变和电解质/液体平衡紊乱。如果不可避免地给予这些药物对，则应密切监测患者。
