Prevalence, risk factors, and outcomes associated with delayed second doses of antibiotics in sepsis at a large academic medical center.

Objective: To evaluate the prevalence, risk factors, and clinical impact of delays in second doses of antibiotics in patients with sepsis. Design: Single-center, retrospective, observational study. Setting: Large teaching hospital. Patients: Adult patients who triggered an electronic sepsis alert in the emergency department (ED), received ≥2 doses of vancomycin or an antipseudomonal beta-lactam, and were discharged with an ICD-10 sepsis code. Methods: We assessed the prevalence of delays in second doses of antibiotics by ≥25% of the recommended dose interval and conducted multivariate regression analyses to assess for risk factors for delays and in-hospital mortality. Results: The cohort included 449 patients, of whom 123 (27.4%) had delays in second doses. In-hospital death occurred in 31 patients (25.2%) in the delayed group and 71 (21.8%) in the non-delayed group (p = 0.44). On multivariate analysis, only location in a non-ED unit at the time second doses were due was associated with delays (OR 2.75, 95% CI 1.20-6.32). In the mortality model, significant risk factors included malignant tumor, respiratory infection, and elevated Sequential Organ Failure Assessment (SOFA) score but not delayed second antibiotic doses (OR 1.19, 95% CI 0.69-2.05). In a subgroup analysis, delayed second doses were associated with higher mortality in patients admitted to non-intensive care units (ICUs) (OR 4.10, 95% CI 1.32-12.79). Conclusions: Over a quarter of patients with sepsis experienced delays in second doses of antibiotics. Delays in second antibiotic doses were not associated with higher mortality overall, but an association was observed among patients admitted to non-ICUs.

Evaluation of Dexmedetomidine as an Adjunct to Phenobarbital for Alcohol Withdrawal in Critically Ill Patients.

INTRODUCTION: Dexmedetomidine (DEX) is commonly used with benzodiazepines for the management of alcohol withdrawal syndrome (AWS), but limited data exist regarding its use with phenobarbital (PHB). This analysis evaluated the utility of DEX in addition to PHB for AWS in adult patients admitted to the intensive care unit (ICU). METHODS: This was a single-center, retrospective cohort analysis of critically ill adult patients who received PHB plus either DEX or different adjunctive therapies (NO-DEX) for AWS between 2018 and 2021. Patients were excluded if they had underlying altered mental status or seizure disorder unrelated to AWS or received PHB at outside hospitals. Coarsened exact matching (CEM) was performed to match patients on baseline characteristics in a 1:1 ratio. The primary outcome was ICU length of stay (LOS). A multivariate linear regression analysis was performed to assess the effects of DEX on ICU LOS when accounting for confounders. Secondary outcomes included days with delirium and incidence of mechanical ventilation after PHB administration. RESULTS: Of the 606 encounters evaluated, 197 met criteria for inclusion. After CEM, 56 encounters remained in each group for analysis. The median ICU LOS was 97.2 [50.1:139.5] hours for the DEX group and 47.5 [28.8:88.1] hours for the NO-DEX group (P = .002). The multivariate linear regression analysis showed the use of DEX (P = .008) was independently associated with an increased ICU LOS by 49.8 h. The DEX group had higher rates of total delirium days (208 vs 143 days, P < .001) and a higher incidence of mechanical ventilation after PHB administration (32% vs 9%, P < .001). CONCLUSION: This analysis suggests the use of adjunctive DEX with PHB for AWS was associated with a prolonged ICU LOS. Additional studies are needed to further understand the role of adjunctive DEX in the treatment of AWS in critically ill patients.

Evaluating the Safety of Continuous Infusion Lidocaine for Postoperative Pain.

OBJECTIVES: The aim was to evaluate the safety of intravenous lidocaine for postoperative pain and the impact on opioid requirements and pain scores. MATERIALS AND METHODS: This was a single-center, retrospective, single-arm analysis of adult patients who received intravenous lidocaine for postoperative pain from January 2016 to December 2019. Patients were excluded if they received lidocaine for any indication other than pain or if lidocaine was only given intraoperatively. The primary outcome of this analysis was to determine the incidence of adverse effects (AEs) and the reason for discontinuation of lidocaine. Secondary outcomes included median daily pain scores (visual analog scale and Critical-Care Pain Observation Tool) and opioid consumption (daily morphine milligram equivalents) 24 hours before infusion and during day 1. RESULTS: A total of 452 patients were evaluated of which 298 (65.9%) patients met inclusion criteria. Of the 154 patients excluded, 153 did not receive lidocaine postoperatively. The median duration of infusion was 34 [20:48] hours with a median initial and maintenance rate of 1 mg/kg/h dosed on ideal body weight. In our analysis, 174 (58.4%) patients had a documented AE during infusion and 38 (12.8%) had lidocaine discontinued because of an AE. The most common AE was nausea in 62 (20.8%) patients and the most common reason for discontinuation was confusion in 8 (2.7%) patients. Daily morphine milligram equivalents (P<0.001) and visual analog scale (P<0.001) significantly decreased when comparing 24 hours before infusion and day 1. CONCLUSION: Although a majority of patients receiving lidocaine for postoperative pain experienced an AE, this did not result in discontinuation in most patients.

Safety of Intravenous Push Lacosamide Compared With Intravenous Piggyback at a Tertiary Academic Medical Center.

BACKGROUND: There are limited data regarding the incidence of adverse events associated with administering lacosamide by intravenous push (IVP) compared with IV piggyback (IVPB). OBJECTIVE: The objective of this analysis was to compare the safety profile, including cardiovascular effects, sedative effects, and IV site reactions of IVP and IVPB lacosamide administration. METHODS: A retrospective pre/post cohort analysis comparing patients who received lacosamide via IVP and IVPB was conducted. Safety end points included hypotension, bradycardia, medication-related sedation, and IV site reactions. The relationship between patient characteristics and the incidence of safety end points was analyzed using the Student t-test and χ2 test as appropriate. RESULTS: Bradycardia occurred after 0.19% of IVP administrations and 1.09% of IVPB administrations assessed (P = 0.07). Hypotension was observed in 3.16% of IVP administrations compared to 1.59% in the IVPB cohort (P = 0.12). Post lacosamide-related sedation was noted in 11.32% and 11.68% of the IVP and IVPB cohorts, respectively (P = 0.87). Infusion site reaction rates of 1.80% and 0.84% were documented in the IVP and IVPB cohorts, respectively (P = 0.33). Of note, only 1 adverse event required clinical intervention. One 200-mg dose in the IVP cohort required a fluid bolus postadministration. CONCLUSION AND RELEVANCE: IVP lacosamide was associated with a similar incidence of cardiovascular, neurological, and infusion site-related adverse events compared with IVPB, in which nearly every adverse event was deemed clinically insignificant. Lacosamide administered via IVP may be considered a safe alternative method of administration in the acute care setting.

Evaluation of the Efficacy and Safety of Inhaled Epoprostenol and Inhaled Nitric Oxide for Refractory Hypoxemia in Patients With Coronavirus Disease 2019.

OBJECTIVES: The objectives of this study were to evaluate the efficacy and safety of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019. DESIGN: Retrospective single-center study. SETTING: ICUs at a large academic medical center in the United States. PATIENTS: Thirty-eight adult critically ill patients with coronavirus disease 2019 and refractory hypoxemia treated with either inhaled epoprostenol or inhaled nitric oxide for at least 1 hour between March 1, 2020, and June 30, 2020. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Of 93 patients screened, 38 were included in the analysis, with mild (4, 10.5%), moderate (24, 63.2%), or severe (10, 26.3%), with acute respiratory distress syndrome. All patients were initiated on inhaled epoprostenol as the initial pulmonary vasodilator and the median time from intubation to initiation was 137 hours (68-228 h). The median change in Pao2/Fio2 was 0 (-12.8 to 31.6) immediately following administration of inhaled epoprostenol. Sixteen patients were classified as responders (increase Pao2/Fio2 > 10%) to inhaled epoprostenol, with a median increase in Pao2/Fio2 of 34.1 (24.3-53.9). The mean change in Pao2 and Spo2 was -0.55 ± 41.8 and -0.6 ± 4.7, respectively. Eleven patients transitioned to inhaled nitric oxide with a median change of 11 (3.6-24.8) in Pao2/Fio2. A logistic regression analysis did not identify any differences in outcomes or characteristics between the responders and the nonresponders. Minimal adverse events were seen in patients who received either inhaled epoprostenol or inhaled nitric oxide. CONCLUSIONS: We found that the initiation of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019, on average, did not produce significant increases in oxygenation metrics. However, a group of patients had significant improvement with inhaled epoprostenol and inhaled nitric oxide. Administration of inhaled epoprostenol or inhaled nitric oxide may be considered in patients with severe respiratory failure secondary to coronavirus disease 2019.

Evaluation of Sedation Outcomes Following Increased Dexmedetomidine Use in the ICU.

To evaluate sedation practices following a dexmedetomidine guideline update in the ICU. DESIGN: Single-center, retrospective chart review. SETTING: Tertiary academic medical center. PATIENTS: Patients were included in this analysis if they were admitted to the ICU and were ordered for continuous infusion sedatives or opioids from September to November 2016 (PRE) and from September to November 2017 (POST). Patients were excluded from this analysis if they met any of the following criteria: mechanical ventilation less than 12 hours, admitted with acute neurologic injury, burn of greater than 20% total body surface area, chronic tracheostomy, admitted to the neuroscience or cardiac surgery ICU, on extracorporeal membrane oxygenation support, or received an infusion of neuromuscular blockers. INTERVENTIONS: Patients admitted during a restricted dexmedetomidine prescribing guideline were compared with patients admitted during an expanded prescribing guideline. MEASUREMENTS AND MAIN RESULTS: Of the 1,426 patients evaluated for inclusion, 427 patients met the criteria in this analysis. Of these, 217 patients were in the PRE and 210 patients in the POST. A majority of patients were excluded for admission to neuroscience or cardiac surgery ICU. Dexmedetomidine was used in 13.8% of encounters in the PRE and 51.9% of encounters in the POST (p < 0.001). The median duration of mechanical ventilation was 49 hours (24-110 hr) in the PRE and 47.5 hours (26-98 hr) in the POST (p = 0.8). ICU length of stay was a median of 136 and 121 hours in the PRE and POST, respectively (p = 0.2). The median hospital length of stay was 296 and 326 hours in the PRE and POST, respectively (p = 0.35). After controlling for possible confounders, ventilation time remained unchanged between the PRE and POST (p = 0.98). CONCLUSIONS: The expansion of a hospital dexmedetomidine prescribing guideline resulted in an increased use of dexmedetomidine but was not associated with a difference in length of mechanical ventilation.