Clinically Relevant Interactions with Anti-Infectives on Intensive Care Units-A Multicenter Delphi Study.

Patients in intensive care units (ICUs) are at high risk of drug-drug interactions (DDIs) due to polypharmacy. Little is known about type and frequency of DDIs within German ICUs. Clinical pharmacists' interventions (PI) recorded in a national database (ADKA-DokuPIK) were filtered for ICU patients. Binary DDIs involving ≥1 anti-infective agent with >1 database entry were selected. A modified two-step Delphi process with a group of senior hospital pharmacists was employed to evaluate selected DDIs for clinical relevance by using a five-point scale and to develop guidance for clinical practice. In total, 16,173 PI were recorded, including 1836 (11%) DDIs in the ICU setting. Of the latter, 41% (756/1836) included ≥1 anti-infective agent, 32% (590/1836) were binary DDIs, and 25% (455/1836) were listed at least twice. This translates into 88 different DDIs, 74% (65/88) of which were rated as being clinically relevant by our expert panel. The majority of DDIs (76% [67/88]) included macrolides, antifungals, or fluoroquinolones. This percentage was even higher in DDIs being rated as clinically relevant by the experts (85% [55/65]). It is noted that an inter-professional discussion and approach is needed in the individual patient management of DDIs. The guidance developed might be a tool for decision support.

The janus-kinase inhibitor ruxolitinib in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 (coronavirus disease 2019), which is associated with high morbidity and mortality, especially in elder patients. Acute respiratory distress syndrome (ARDS) is a life-threatening complication of COVID-19 and has been linked with severe hyperinflammation. Dexamethasone has emerged as standard of care for COVID-19 associated respiratory failure. In a non-randomized prospective phase II multi-center study, we asked whether targeted inhibition of Janus kinase-mediated cytokine signaling using ruxolitinib is feasible and efficacious in SARS-CoV-2- induced ARDS with hyperinflammation. Sixteen SARS-CoV-2 infected patients requiring invasive mechanical ventilation for ARDS were treated with ruxolitinib in addition to standard treatment. Ruxolitinib treatment was well tolerated and 13 patients survived at least the first 28 days on treatment, which was the primary endpoint of the trial. Immediate start of ruxolitinib after deterioration was associated with improved outcome, as was a lymphocyte-to-neutrophils ratio above 0.07. Together, treatment with the janus-kinase inhibitor ruxolitinib is feasible and might be efficacious in COVID-19 induced ARDS patients requiring invasive mechanical ventilation. The trial has been registered under EudraCT-No.: 2020-001732-10 and NCT04359290.

A new approach on assessing clinical pharmacists' impact on prescribing errors in a surgical intensive care unit.

Background With a clinical pharmacists' participation in an intensive care unit (ICU) previous international studies have shown a reduction of medication errors, drug costs and improvements of clinical outcomes. Still there is a lack of qualitative data on clinical pharmacists' impact on prescribing error rates in the ICU. Therefore, a new approach was developed relating prescribing errors to the number of monitored medications including physicians' approval on all prescribing errors. Objective This study investigates the influence of clinical pharmacists' medication review on the prescribing error rate in an ICU. Setting A controlled interventional study was conducted in a surgical ICU with one control phase (P0) and two intervention phases (P1 and P2). Method The investigation aimed to determine if the medication review by clinical pharmacists results in a significant reduction of prescribing errors related to a control period. In contrast to previous studies, prescribing errors detected by the clinical pharmacists, were only taken into account, if consent with the physicians was achieved. Secondary outcomes were the reduction of potentially severe prescribing errors, the number of days without systemic anti-infective therapy and the ICU length of stay. Throughout P0 the data was collected retrospectively without any intervention. During the intervention periods P1 and P2, two clinical pharmacists screened the medical records for prescribing errors and discussed them with the senior physician in charge. During P2 one clinical pharmacist attended ward rounds additionally. Main Outcome Measure The main outcome measure of this study was the number of prescribing errors detected related to the number of monitored medications. Results The incidence of prescribing errors was significantly reduced from 1660 in P0 to 622 in P1 respectively 401 in P2 (P0 vs. P1/P2 respectively; both p < 0.001; Fisher's Exact Test) in total, respective 14.12% in P0 vs. 5.13% in P1 and 3.25% in P2 related to the monitored medications (P0:11755; P1:12134; P2:12329). Conclusion Clinical pharmacists' interventions led to a significant reduction of prescribing errors in the ICU, contributing to a safer medication process. We strongly recommend a broad implementation of clinical pharmacists in ICUs.