Outcomes of Intravenous Push versus Intermittent Infusion Administration of Cefepime in Critically Ill Patients.

The equivalence of intravenous push (IVP) and piggyback (IVPB) administration has not been evaluated in the critically ill population for most medications, but it is especially relevant for antibiotics, such as cefepime, that exhibit time-dependent bactericidal activity. A single center, retrospective, observational pre/post-protocol change study included critically ill adults who received cefepime as empiric therapy between August 2015 and 2021. The primary outcome was treatment failure, which was defined as a composite of escalation of antibiotic regimen or all-cause mortality. Secondary outcomes included adverse drug events, days of cefepime therapy, total days of antibiotic therapy, and ICU and hospital length of stay. Outcomes were compared using Chi-squared, Mann Whitney U, and binary logistic regression as appropriate. A total of 285 patients were included: 87 IVPB and 198 IVP. Treatment failure occurred in 18% (n = 16) of the IVPB group and 27% (n = 54) of the IVP group (p = 0.109). There were no significant differences in secondary outcomes. Longer duration of antibiotics (odds ratio [OR] 1.057, 95% confidence interval [CI] 1.013-1.103), SOFA score (OR 1.269, 95% CI 1.154-1.397) and IVP administration of cefepime (OR 2.370, 95% CI 1.143-4.914) were independently associated with treatment failure. Critically ill patients who received IVP cefepime were more likely to experience treatment failure in an adjusted analysis. The current practice of IVP cefepime should be reevaluated, as it may not provide similar clinical outcomes in the critically ill population.

Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome.

Background: Inhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States. Methods: This was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation. Outcomes included oxygenation parameters, physician-rated Clinical Global Impression-Improvement (CGI-I) scale scores, and adverse events. Response to iNO was defined as >20% improvement in P/F ratio. Results: Thirty-seven patients at six sites were included. A P/F ratio of ≤100 was the most common reason for exclusion (n=146; 83% of excluded patients). The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after iNO initiation. The response rate was 62% (n=23). During hospitalization, no patient experienced adverse events, including methemoglobinaemia, airway injury, or worsening pulmonary oedema associated with iNO. At discharge, 54.0% (n=20) of patients improved or remained stable according to the CGI-I. Conclusion: In patients hospitalized with COVID-19 and mild-to-moderate ARDS, iNO was associated with improvement in the P/F ratio with no reported toxicity. This study provides additional evidence supporting a favourable benefit-risk profile for iNO in the treatment of mild-to-moderate ARDS in patients with COVID-19 infection.