Impact of Sedation Practices on Mortality in COVID-19-Associated Adult Respiratory Distress Syndrome Patients: A Multicenter Retrospective Descriptive Study.

Background: Reduction in sedation exposure is an important metric in intensive care unit (ICU) patients. However, challenges arose during the coronavirus disease-2019 (COVID-19) pandemic in adhering to this practice, driven by concerns on transmission and disease severity issues. Accordingly, diverse sedation approaches emerged, although the effect on mortality has not been studied thoroughly. Methods: Retrospective cohort study in the medical ICU of seven hospitals within a major Health System in Northeast Ohio. We included all adult patients admitted with COVID-19 requiring invasive mechanical ventilation (IMV) from March 2020 to December 2021. Results: Study included 2394 COVID-19 patients requiring IMV. Across waves, sample included 55-63% male subjects, with an average age of 61-68 years (P < 0.001), Acute Physiologic and Chronic Health Evaluation (APACHE)-III score 65.8-68.9 (P = 0.37), median IMV duration 8-10 days (P = 0.14), and median ICU duration 9.8-11.6 days (P = 0.084). Propofol remained the primary sedative (84-92%; P = 0.089). Ketamine use increased from the first (9.7%) to fourth (19%) wave (P = 0.002). Midazolam use decreased from the first (27.4%) to third (9.4%) wave (P = 0.001). Dexmedetomidine use declined from 35% to 27-28% (P = 0.002) after the first wave. A multivariable regression analysis indicated clinical variables explained 34% of the variation in hospital mortality (R2). Factors associated with higher mortality included age [aOR = 1.059 (95% CI 1.049-1.069); P < 0.001], COVID-19 wave, especially fourth wave [aOR = 2.147, (95% CI 1.370-3.365); P = 0.001], and higher number of vasopressors [aOR = 31.636, (95% CI 17.603-56.856); P < 0.001]. Addition of sedative medications to a second model led to an increase in the R2 by only 1.6% to 35.6% [aOR = 1 (95% CI 1-1); P > 0.05] for propofol, ketamine, and midazolam. Dexmedetomidine demonstrated a decrease in the odds of mortality [aOR = 0.96 (95% CI 0.94-0.97); P < 0.001]. Conclusion: Mortality in critical COVID-19 patients was mostly driven by illness severity, and the choice of sedation might have minimal impact when other factors are controlled.

Antipsychotic Use for ICU Delirium and Associated Inflammatory Markers.

Purpose: We sought to evaluate critically ill patients with delirium to evaluate inflammatory cytokine production and delirium progression and the role of antipsychotics. Materials and Methods: Adult critically ill patients with confirmed delirium according to a positive CAM-ICU score were included and IL-6 and IL-8 levels were trended for 24 h in this single-center, prospective, observational cohort study. Results: A total of 23 patients were consented and had blood samples drawn for inclusion. There was no difference in IL-6 and IL-8 levels at baseline, 4 to 8 h, and 22 to 28 h after enrollment when comparing patients based on antipsychotic exposure. We identified 2 patient clusters based on age, APACHE III, need for mechanical ventilation, and concomitant infection. In cluster 1, 5 (33.3%) patients received antipsychotics versus 5 (62.5%) patients in cluster 2 (P = .18). Patients in cluster 1 had more co-inflammatory conditions (P < .0001), yet numerically lower baseline IL-6 (P = .18) and IL-8 levels (P = .80) compared to cluster 2. Patients in cluster 1 had a greater median number of delirium-free days compared to cluster 2 (17.0 vs 6.0 days; P = .05). Conclusions: In critically ill patients with delirium, IL-6 and IL-8 levels were variable and antipsychotics were not associated with improvements in delirium or inflammatory markers.

Antibody-Mediated Rejection Management Following Lung Transplantation.

BACKGROUND: Although antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited. OBJECTIVE: The purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients. METHODS: This single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019. RESULTS: A total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter. CONCLUSION AND RELEVANCE: This represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.

Prescribing Practices of Valproic Acid for Agitation and Delirium in the Intensive Care Unit.

BACKGROUND: Analgesics, sedatives, and antipsychotics are commonly prescribed for agitation and delirium in the intensive care unit (ICU), but their use is limited by adverse effects and lack of efficacy. Valproic acid is an alternative treatment option. OBJECTIVE: The primary objective of this study was to describe valproic acid prescribing in our institution's ICUs when used for agitation or delirium. Measures of effectiveness and safety were also assessed. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study of adult inpatients admitted to the ICU between January 2018 and August 2018. Patients who received valproic acid for the treatment of agitation or delirium for ≥24 hours were included. Prescribing practices were evaluated for dose, frequency, and route of administration. Effectiveness was assessed via agitation and delirium assessment tools and quantity of adjunctive agents used. RESULTS: A total of 80 patients were included, with 35 receiving valproic acid alone and 45 in conjunction with antipsychotics. The most common valproic acid regimen was 250 mg orally 3 times daily. Delirium resolution occurred in 55% of patients: 24 in the valproic acid monotherapy group and 20 in the valproic acid plus antipsychotic group (69% vs 44%; P = 0.03). The incidence of delirium decreased from valproic acid day 0 to day 3 (93% vs 68%; P < 0.01), with no change in agitation (64% vs 63%; P = 0.28). CONCLUSION AND RELEVANCE: Valproic acid is frequently prescribed in agitated, delirious patients at our institution and may have a role in the management of ICU delirium.

Effectiveness, Safety, and Economic Comparison of Inhaled Epoprostenol Brands, Flolan and Veletri, in Acute Respiratory Distress Syndrome.

Background: No previous studies exist examining 2 inhaled epoprostenol formulations in an acute respiratory distress syndrome (ARDS) patient population. Objective: The study aim was to evaluate a formulary conversion from inhaled Flolan to Veletri to determine the impact on effectiveness, safety, and cost in patients with ARDS. Methods: This was a single-center, retrospective, matched cohort observational study at a tertiary care academic medical center. Patients included were mechanically ventilated, adult patients with ARDS receiving inhaled Flolan or Veletri for ≥1 hour in the intensive care unit. Results: A total of 132 patients were included in the matched cohort. There was no difference detected in change in partial pressure of arterial O2/fraction of inspired O2 (PaO2/FiO2) ratio after 1 hour of therapy between the inhaled Flolan and Veletri groups (27.2 ± 46.2 vs 30 ± 68 mm Hg, P = 0.78). Significant differences in secondary outcomes included incidence of hypotension (83% vs 95.5%, P = 0.04) and thrombocytopenia (9.1% vs 29.5%, P < 0.01) in the inhaled Flolan and Veletri groups, respectively, with no difference in cost per duration of therapy (P = 0.29). Conclusions and Relevance: There was no difference in the change in PaO2/FiO2 ratio after 1 hour of therapy between inhaled Flolan and Veletri in an ARDS patient population. The formulary conversion from inhaled Flolan to Veletri was likely justified.

Evaluation of Albumin 25% Use in Critically Ill Patients at a Tertiary Care Medical Center.

Background: Albumin 25% has been studied and has demonstrated benefit in a limited number of patient populations. The use of albumin 25% is associated with higher costs compared with crystalloid therapy. The aim of this study was to describe the prescribing practices of albumin 25% at a tertiary-care medical center and identify opportunities for restriction criteria related to its use to help generate cost savings. Methods: This evaluation was a retrospective, noninterventional, descriptive study of albumin 25% use between June 2015 and February 2016. Inclusion criteria consisted of patients ≥18 years old and who received at least one dose of albumin 25% while admitted to a Cleveland Clinic main campus intensive care unit (ICU). Inclusion was restricted to 150 randomly selected patients. Results: A total of 539 albumin 25% orders were placed for the 150 included patients. The cardiovascular ICU more frequently prescribed albumin 25% compared with the medical, surgical, neurosciences, and coronary ICUs (51% vs 23% vs 11% vs 9% vs 6%, respectively). Although the cardiovascular surgery ICU most frequently prescribed albumin 25% compared with other ICUs, the medical ICU prescribed a larger total quantity of albumin 25% compared with the cardiovascular, surgical, neurosciences, and coronary ICUs (8705 g vs 7275 g vs 3205 g vs 2162 g vs 625 g, respectively). The majority of patients (61%) did not have an indication listed for albumin 25% use and only 9% of patients were prescribed for indications supported by primary literature. Of the patients prescribed albumin for other indications not supported by primary literature (30%), the most common reasons for albumin 25% were hypotension, acute kidney injury, and volume resuscitation. The median cost per patient of albumin 25% was $417 with a total cost of $122 164 for the cohort. Only 19% of the total cost aligned with dosing regimens evaluated in primary literature. Conclusion: Prescribing patterns of albumin 25% at a tertiary academic medical center do not align with indications supported by primary literature. These findings identified a major opportunity for prescriber education and implementation of restriction criteria to target cost savings.

Sedation Variability Increases Incidence of Delirium in Adult Medical Intensive Care Unit Patients at a Tertiary Academic Medical Center.

BACKGROUND: Variability in sedation may increase the incidence of delirium and mortality, as well as increased intensive care unit (ICU) and hospital lengths of stay (LOS), despite mean Richmond Agitation Sedation Scale (RASS) scores at goal. Coefficient of variation (CV) can be used to represent variability with a higher ratio indicating increased variability. STUDY QUESTION: Do patients with an increased variability in sedation, as evaluated by CV in RASS, have an increased incidence of delirium? METHODS: We conducted a retrospective chart review of adult medical ICU patients requiring mechanical ventilation (MV) for ≥24 hours between January and April 2013. Patients were excluded if intubated at an outside hospital, neuromuscularly blocked, suffering from anoxic brain injury, or had a goal RASS of -4 or -5. Outcomes assessed included the presence of delirium, as evaluated by the Confusion Assessment Method, RASS, CV in RASS, duration of MV, ICU, and hospital LOS, and survival. RESULTS: Of 45 included patients, 32 experienced delirium during their ICU admission and 13 did not. The groups were similar at baseline. There was no difference in mean RASS when comparing the delirium and nondelirium groups (-1.6 ± 1.3 vs. -1.8 ± 0.8, respectively; P = 0.61). Patients with delirium had a greater CV in RASS (0.3 ± 0.135 vs. 0.2 ± 0.105; P = 0.02), a longer MV duration [4 (2-8) vs. 3 (2-3) days; P = 0.045], and a trend toward increased ICU LOS [8 (5-12.25) vs. 4 (3-8) days; P = 0.096], but no difference in hospital LOS [13 (10-25) vs. 18 (9-39) days; P = 0.83] and survival (71.9% vs. 69.2%; P = 1.0). CONCLUSION: Medical ICU patients with delirium had a higher CV in RASS compared with patients without delirium, suggesting that greater variability in sedation may increase the incidence of delirium. Patients with delirium also had a greater duration of MV and a trend toward longer ICU LOS.

Correction to: Clinical predictors of renal non-recovery in acute respiratory distress syndrome.

Following publication of the original article.

Clinical predictors of renal non-recovery in acute respiratory distress syndrome.

BACKGROUND: Acute kidney injury (AKI) is the most common extra-pulmonary organ failure in acute respiratory distress syndrome (ARDS). Renal recovery after AKI is determined by several factors. The objective of this study was to determine the predictors of renal non-recovery in ARDS patients. METHODS: A single center retrospective cohort study of patients with AKI after onset of ARDS. Patients with preexisting chronic kidney disease or intensive care unit stay < 24 h were excluded. AKI staging was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Renal non-recovery was defined as death, dialysis dependence, serum creatinine ≥1.5 times the baseline, or urine output < 0.5 mL/kg/h more than 6 h. RESULTS: Of the 244 patients that met study criteria, 60 (24.6%) had stage I AKI, 66 (27%) had stage II AKI, and 118 (48.4%) had stage III AKI. Of those, 148 (60.7%) patients had renal non-recovery. On multivariable analysis, factors associated with renal non-recovery were a higher stage of AKI (odds ratio [OR] stage II 5.71, 95% confidence interval [CI] 2.17-14.98; OR stage III 45.85, 95% CI 16.27-129.2), delay in the onset of AKI (OR 1.12, 95% CI 1.03-1.21), history of malignancy (OR 4.02, 95% CI 1.59-10.15), septic shock (OR 3.2, 95% CI 1.52-6.76), and a higher tidal volume on day 1-3 of ARDS (OR 1.41, 95% CI 1.05-1.90). Subgroup analysis of survival at day 28 of ARDS also found that higher severity of AKI (OR stage II 8.17, 95% CI 0.84-79.91; OR stage III 111.67, 95% CI 12.69-982.91), delayed onset of AKI (OR 1.12, 95% CI 1.02-1.23), and active malignancy (OR 6.55, 95% CI 1.34-32.04) were significant predictors of renal non-recovery. CONCLUSIONS: A higher stage of AKI, delayed onset of AKI, a history of malignancy, septic shock, and a higher tidal volume on day 1-3 of ARDS predicted renal non-recovery in ARDS patients. Among survivors, a higher stage of AKI, delayed onset of AKI, and a history of malignancy were associated with renal non-recovery.