Faculty Bibliography

BACKGROUND/UNASSIGNED:Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. OBJECTIVE/UNASSIGNED:The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. METHODS/UNASSIGNED:A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. RESULTS/UNASSIGNED:This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. CONCLUSION AND RELEVANCE/UNASSIGNED:Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Ultrasound enhancing agents (UEAs) are medications that enable clear visualization of ultrasound images. While large studies have demonstrated the safety of these agents, case reports of life-threatening reactions temporally associated with their use have been published and reported to the Food and Drug Administration. Current literature describes the most serious adverse reactions due to UEAs to be allergic in nature; however, embolic phenomena may play a role as well. Here, we report a case of unexplained cardiac arrest following the administration of sulfur hexafluoride (Lumason^®) in an adult inpatient undergoing echocardiography where resuscitative efforts were ultimately unsuccessful, and review possible mechanisms of cardiac arrest based on prior published literature.

The need for therapeutic drug monitoring of direct oral anticoagulants (DOACs) remains an area of clinical equipoise. Although routine monitoring may be unnecessary given predictable pharmacokinetics in most patients, there may be altered pharmacokinetics in those with end organ dysfunction, such as those with renal impairment, or with concomitant interacting medications, at extremes of body weight or age, or in those with thromboembolic events in atypical locations. We aimed to assess real-world practices in situations in which DOAC drug-level monitoring was used at a large academic medical center. A retrospective review of the records of patients who had a DOAC drug-specific activity level checked from 2016 to 2019 was included. A total of 119 patients had 144 DOAC measurements (apixaban (n = 62) and rivaroxaban (n = 57)). Drug-specific calibrated DOAC levels were within an expected therapeutic range for 110 levels(76%), with 21 levels (15%) above the expected range and 13 levels (9%) below the expected range. The DOAC levels were checked in the setting of an urgent or emergent procedure in 28 patients (24%), followed by renal failure in 17 patients (14%), a bleeding event in 11 patients (9%), concern for recurrent thromboembolism in 10 patients (8%), thrombophilia in 9 patients (8%), a history of recurrent thromboembolism in 6 patients (5%), extremes of body weight in 7 patients (5%), and unknown reasons in 7 patients (5%). Clinical decision making was infrequently affected by the DOAC monitoring. Therapeutic drug monitoring with DOACs may help predict bleeding events in elderly patients, those with impaired renal function, and in the event of an emergent or urgent procedure. Future studies are needed to target the select patient-specific scenarios where monitoring DOAC levels may impact clinical outcomes.

Background and Purpose: Increased intracranial pressure due to cerebral edema is a medical emergency in which 23.4% sodium chloride (23.4% NaCl) may be a lifesaving intervention. Currently, safety data is limited on slow IV push (IVP) administration. The purpose of this study was to evaluate the safety of IVP administration of 23.4% NaCl and determine the number of infusion-related adverse events (IRAEs) compared to slow IV infusion (SIV) administration. Methods: We performed a retrospective review of patients who received a dose of 23.4% NaCl at the (removed institution) from January 2015 to June 2020 as either SIV over 30 minutes or IVP over 2-5 minutes. Results: In total, 81 patients, 55 in the IVP group and 26 in the SIV group, were included in the analysis. There was a significantly faster time from order entry to dose completion (IVP 25 [13,58] vs SIV 73 [55,113] minutes, P <.001). There was no difference in IRAEs between the groups (IVP 17 [31%] vs SIV 6 [23%], P =.466). Hypotension was most common (IVP 13 [24%] vs SIV 5 [19%], P =.656) followed by bradycardia (IVP 6 [11%] vs SIV 1 [4%], P =.291). There were no extravasations reported. Conclusions: Overall, among a cohort of patients with cerebral edema, we found no difference in the incidence of IRAEs between SIV and IVP administration of 23.4% NaCl, and found a faster time to complete administration fssor the latter. In emergent scenarios where time may impact neurologic function, 23.4% NaCl administered IVP may be an alternative to SIV administration.

BACKGROUND:Advances in cancer therapeutics have improved overall survival and prognosis in this patient population; however, this has come at the expense of cardiotoxicity including arrhythmia. SUMMARY:Cancer and its therapies are associated with cardiotoxicity via several mechanisms including inflammation, cardiomyopathy, and off-target effects. Among cancer therapies, anthracyclines and tyrosine kinase inhibitors (TKIs) are particularly known for their pro-arrhythmia effects. In addition to cardiomyopathy, anthracyclines may be pro-arrhythmogenic via reactive oxygen species (ROS) generation and altered calcium handling. TKIs may mediate their cardiotoxicity via inhibition of off-target tyrosine kinases. Ibrutinib-mediated inhibition of CSK may be responsible for the increased prevalence of atrial fibrillation. Further investigation is warranted to further elucidate the mechanisms behind arrhythmias in cancer therapies. KEY MESSAGES:Arrhythmias are a common cardiotoxicity of cancer therapies. Cancer therapies may induce arrhythmias via off-target effects. Understanding the mechanisms underlying arrhythmogenesis associated with cancer therapies may help design cancer therapies that can avoid these toxicities.

OBJECTIVE:concentration after KCl administration) and assess the incidence of hyperkalemia. METHODS:This single-center, retrospective study evaluated infants and children who received parenteral KCl supplementation of 0.5 or 1 mEq/kg between January 2017 and December 2019. RESULTS:compared with those who had a concentration drawn after this time frame (0.8 vs 0.6 mEq/L; p < 0.01). CONCLUSIONS:of 0.8 and 0.5 mEq/L, respectively, in non-cardiac pediatric patients, with low observed incidence of hyperkalemia.

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Background/UNASSIGNED:Patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) have poor outcomes and frequently develop comorbid conditions, including cytomegalovirus (CMV) reactivation. The implications of CMV reactivation in this setting are unknown. We aimed to investigate if treatment of CMV viremia improved in-hospital mortality in ICU patients with COVID-19. Methods/UNASSIGNED:In this single-center retrospective study, we analyzed clinical outcomes in patients diagnosed with COVID-19 pneumonia and CMV viremia admitted to an ICU from March 1, 2020, to April 30, 2021, who either received treatment (ganciclovir and/or valganciclovir) or received no treatment. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were total hospital length of stay (LOS), ICU LOS, requirement for extracorporeal membrane oxygenation (ECMO) support, duration of mechanical ventilation (MV), and predictors of in-hospital mortality. Results/UNASSIGNED: = .749). There was no significant difference in hospital LOS, though CMV-treated patients had a longer ICU LOS. Conclusions/UNASSIGNED:Treatment of CMV viremia did not decrease in-hospital mortality in ICU patients with COVID-19, but the sample size was limited. CMV viremia was significantly associated with total steroid dose received and longer ICU stay.

Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year.