A contemporary analysis of 20,086 deceased donor liver biopsies.

BACKGROUND: Pre-transplant deceased donor liver biopsy may impact decision making; however, interpretation of the results remains variable and depends on accepting center practice patterns. METHODS: In this cohort study, adult recipients from 04/01/2015-12/31/2020 were identified using the UNOS STARfile data. The deceased donor liver biopsies were stratified by risk based on degree of fibrosis, macrovesicular fat content, and level of portal infiltration (low-risk: no fibrosis, no portal infiltrates, and <30% macrosteatosis; moderate-risk: some fibrosis or mild infiltrates and <30% macrosteatosis; high-risk: most fibrosis, moderate/marked infiltrates, or ≥30% macrosteatosis). Graft utilization, donor risk profile, and recipient outcomes were compared across groups. RESULTS: Of the 51,094 donor livers available, 20,086 (39.3%) were biopsied, and 34,606 (67.7%) were transplanted. Of the transplanted livers, 14,908 (43.1%) were biopsied. The transplanted grafts had lower mean macrovesicular fat content (9.3% transplanted vs. 26.9% non-transplanted, P < 0.001) and less often had any degree of fibrosis (20.9% vs. 39.9%, P < 0.001) or portal infiltration (51.3% vs. 58.2%, P < 0.001) versus non-transplanted grafts. Post-transplant recipient LOS (14.2 days high-risk vs. 15.2 days low-risk, P = 0.170) and 1-year graft survival (90.5% vs. 91.7%, P = 0.137) did not differ significantly between high- versus low-risk groups. Kaplan-Meier survival estimates further revealed no differences in the 5-year graft survival across risk strata (P = 0.833). Of the 5178 grafts biopsied and turned down, PSM revealed 1338 (26.0%) were potentially useable based on biopsy results and donor characteristics. CONCLUSION: Carefully matched deceased donor livers with some fibrosis, inflammation, or steatosis ≥30% may be suitable for transplantation. Further study of this group of grafts may decrease turndowns of potentially useable organs.

Peripheral Administration of Norepinephrine: A Prospective Observational Study.

BACKGROUND: Historically, norepinephrine has been administered through a central venous catheter (CVC) because of concerns about the risk of ischemic tissue injury if extravasation from a peripheral IV catheter (PIVC) occurs. Recently, several reports have suggested that peripheral administration of norepinephrine may be safe. RESEARCH QUESTION: Can a protocol for peripheral norepinephrine administration safely reduce the number of days a CVC is in use and frequency of CVC placement? STUDY DESIGN AND METHODS: This was a prospective observational cohort study conducted in the medical ICU at a quaternary care academic medical center. A protocol for peripheral norepinephrine administration was developed and implemented in the medical ICU at the study site. The protocol was recommended for use in patients who met prespecified criteria, but was used at the treating clinician's discretion. All adult patients admitted to the medical ICU receiving norepinephrine through a PIVC from February 2019 through June 2021 were included. RESULTS: The primary outcome was the number of days of CVC use that were avoided per patient, and the secondary safety outcomes included the incidence of extravasation events. Six hundred thirty-five patients received peripherally administered norepinephrine. The median number of CVC days avoided per patient was 1 (interquartile range, 0-2 days per patient). Of the 603 patients who received norepinephrine peripherally as the first norepinephrine exposure, 311 patients (51.6%) never required CVC insertion. Extravasation of norepinephrine occurred in 35 patients (75.8 events/1,000 d of PIVC infusion [95% CI, 52.8-105.4 events/1,000 d of PIVC infusion]). Most extravasations caused no or minimal tissue injury. No patient required surgical intervention. INTERPRETATION: This study suggests that implementing a protocol for peripheral administration of norepinephrine safely can avoid 1 CVC day in the average patient, with 51.6% of patients not requiring CVC insertion. No patient experienced significant ischemic tissue injury with the protocol used. These data support performance of a randomized, prospective, multicenter study to characterize the net benefits of peripheral norepinephrine administration compared with norepinephrine administration through a CVC.

A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients.

BACKGROUND: Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU. RESEARCH QUESTION: Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury? STUDY DESIGN AND METHODS: This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission. RESULTS: Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy. INTERPRETATION: VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU.

Association of 48-h net fluid status with change in renal function and dyspnea among patients with decompensated heart failure: A pooled cohort analysis of three acute heart failure trials.

BACKGROUND: Acute heart failure (AHF) exacerbations are a leading cause of hospitalization in the United States. Despite the frequency of AHF hospitalizations, there are inadequate data or practice guidelines on how quickly diuresis should be achieved. OBJECTIVE: To study the association of 48-h net fluid change and (A) 72-h change in creatinine and (B) 72-h change in dyspnea among patients with acute heart failure. DESIGNS, SETTINGS, AND PARTICIPANTS: This is a retrospective, pooled cohort analysis of patients from the DOSE, ROSE, and ATHENA-HF trials. INTERVENTIONS: The primary exposure was 48-h net fluid status. MAIN OUTCOMES AND MEASURES: The co-primary outcomes were 72-h change in creatinine and 72-h change in dyspnea. The secondary outcome was risk of 60-day mortality or rehospitalization. RESULTS: Eight hundred and seven patients were included. The mean 48-h net fluid status was -2.9 L. A nonlinear association was observed with net fluid status and creatinine change, such that creatinine improved with each liter net negative up to 3.5 L (-0.03 mg/dL per liter negative [95% confidence interval [CI]: -0.06 to -0.01) and remained stable beyond 3.5 L (-0.01 [95% CI: -0.02 to 0.001], p = .17). Net fluid loss was associated with a monotonic improvement of dyspnea (1.4-point improvement per liter negative [95% CI: 0.7-2.2], p = .0002). Each liter net negative by 48 h was also associated with 12% decreased odds of 60-day rehospitalization or death (odds ratio: 0.88; 95% CI: 0.82-0.95; p = .002). CONCLUSION: Aggressive net fluid targets within the first 48 h are associated with effective relief of patient self-reported dyspnea and improved long-term outcomes without adversely affecting renal function.

Clinical Utilization of Stress Dose Hydrocortisone in Adult Patients With Septic Shock: A Retrospective Observational Study at a Large Academic Medical Center.

Background: The use of stress dose corticosteroids, specifically, hydrocortisone, in septic shock is heterogeneous, and current clinical trials yield conflicting results. Regardless, they are still recommended by guidelines for vasopressor-dependent septic shock. Objectives: This study sought to characterize current practice of hydrocortisone use in patients with septic shock and secondarily to compare clinical outcomes of those who received hydrocortisone to those who did not. Methods: This single center, retrospective cohort study evaluated patients with septic shock admitted to a tertiary care center between 2012 and 2017. Patients receiving hydrocortisone for at least two doses were compared to those without. Results: 3411 septic shock patients were included; 1593 (47%) received hydrocortisone and 1818 (53%) did not. Patients who received hydrocortisone had higher lactate (4.0 vs 3.4 mmol/L; P < .01) and Acute Physiology and Chronic Health Evaluation (APACHE) III scores (104.1 vs 91.0; P < .01). Vasopressor duration was 1.7 days longer in the hydrocortisone group (P < .01), and the hydrocortisone group had higher hospital mortality (52% vs 38%; P < .01). A propensity score-matched population was conducted in patients with APACHE scores >100: vasopressor duration was longer in those who received hydrocortisone (3.9 vs 2.0 days; P < .01), and hospital mortality was higher (59.3% vs 53.1%; P = .036); however, after multivariable adjustment, no association between receipt of hydrocortisone and hospital mortality was detected (OR 1.2 [95% CI .9-1.6]). Conclusions: Patients who received hydrocortisone were more severely ill than those that did not, making retrospective evaluation of this question challenging. These results highlight the wide variability and heterogeneity in hydrocortisone use in clinical practice.

Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock.

INTRODUCTION: Clinical studies evaluating the use of hydrocortisone in patients with septic shock are heterogeneous in design with conflicting results. The appropriate time in which to initiate hydrocortisone after shock onset is unknown. This study sought to compare clinical outcomes including vasopressor duration and mortality in patients with septic shock who received hydrocortisone based on timing of initiation after shock onset. METHODS: Retrospective cohort study of patients between 2011 and 2017 admitted to 10 medical, surgical, and neurosciences intensive care units (ICUs) at a large, tertiary care academic medical center. Adult patients with vasopressor-dependent septic shock who received hydrocortisone were included. Patients were divided into five timing cohorts based on time after shock onset: 0-6, 6-12, 12-24, 24-48, or >48 h. The primary outcome was days alive and free from vasopressors. RESULTS: One thousand four hundred seventy patients were included: 567 (38.6%) received hydrocortisone between 0 and 6 h, 231 (15.7%) 6 and 12 h, 260 (17.7%) 12 and 24 h, 195 (13.3%) 24 and 48 h, and 217 (14.8%) >48 h after shock onset. Patients who received hydrocortisone earlier were sicker at baseline with higher APACHE III scores, lactate concentrations, and norepinephrine requirements. On univariate analysis, days alive and free from vasopressors did not significantly differ amongst the timing groups (median 3.3 days for 0-6 h; 1.9 for 6-12 h; 1.9 for 12-24 h; 0 for 24-48 h; 0 for >48 h; P = 0.39); similarly, ICU mortality did not differ. On multivariable linear regression, timing of hydrocortisone was independently associated with more days alive and free from vasopressors when comparing initiation within 0 to 6 h with >48 h (beta-coefficient 2.8 days [95% CI 0.8-4.7]), 6-12 h with >48 h (2.5 days [95% CI 0.2-4.7]), and 12-24 h with >48 h (2.3 days [95% CI 0.2-4.5]). On multivariable logistic regression, timing of hydrocortisone was associated with reduced ICU mortality when comparing receipt within 0 to 6 h of shock onset to >48 h after shock onset (OR 0.6, 95% CI 0.4-0.8). CONCLUSIONS: In patients in whom hydrocortisone is prescribed for vasopressor-dependent septic shock, timing is crucial and hydrocortisone should be started within the first 12 h after shock onset.

New-onset atrial fibrillation is an independent predictor of mortality in medical intensive care unit patients.

BACKGROUND: Atrial fibrillation (AF) has been extensively studied in postoperative critically ill surgical patients, but little literature exists to describe the outcomes of patients in the medical intensive care unit (ICU). OBJECTIVES: To determine the incidence of new-onset AF in patients admitted to a medical ICU and if new-onset AF was associated with adverse clinical outcomes. METHODS: This was a single-center, retrospective study of all adult patients admitted to the medical ICU at an academic medical center for >24 hours between December 2008 and April 2010. Collected data included past medical history, incidence of new-onset AF, Acute Physiology and Chronic Health Evaluation II scores, organ failure, length of stay in the ICU and hospital, and in-hospital and 60-day survival. RESULTS: A total of 741 patients were included. New-onset AF occurred in 53 patients (7.2%). In-hospital mortality was significantly greater for patients with new-onset AF (45% vs 16%; adjusted odds ratio [OR] = 2.21, 95% CI 1.07-4.54, P = 0.032), as was 60-day mortality (51% vs 23%; adjusted OR = 1.99, 95% CI = 1.01-3.91, P = 0.047). Patients with new-onset AF experienced greater ICU (6 ± 10.2 days vs 3 ± 3.6 days, P < 0.01) and hospital (15 ± 19 days vs 7 ± 9 days, P < 0.01) lengths of stay. CONCLUSIONS: Medical ICU patients who developed new-onset AF experienced a 2-fold increase in the odds of in-hospital mortality and death at 60 days. Further research investigating contributing factors to new-onset AF and potential treatments is warranted.

An assessment of patient and pharmacist knowledge of and attitudes toward reporting adverse drug events due to formulation switching in patients with epilepsy.

A survey was developed to gather information from both patients with epilepsy and community pharmacists on the issue of antiepileptic drug (AED) formulation switching, which includes brand to generic, generic to brand, and generic to generic. Data were obtained from 82 patients (or parents of patients) with epilepsy and 112 community pharmacists. More than 92% of patients and 85% of pharmacists agreed that switching between forms of the same AEDs may cause an increase in seizures or adverse effects. More than two-thirds of our patient sample reported having problems with formulation switching; many also reported knowing other patients with problems. Just more than half (51%) of the pharmacists knew of patients who have described problems when they have changed AED formulations. Less than 50% of both populations knew that problems resulting from formulation switching should be reported as adverse drug events to the FDA. Not many pharmacists and far fewer patients use MedWatch to report these problems. We conclude that both patients with epilepsy and pharmacists are underinformed and underinvolved with reporting adverse drug events.