Faculty Bibliography

INTRODUCTION/BACKGROUND:The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. METHODS:This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. RESULTS:A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. CONCLUSION/CONCLUSIONS:We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy (DAPT) is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients that had PCI within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event (MACE). Secondary outcomes included VerifyNow® platelet reactivity units (PRU) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42, 45%), followed by NPO status (26, 28%), and MCS alone (22, 24%). The primary outcome of MACE occurred in one patient (1.1%). Out of 92 patients, 77% had a P2Y12 level collected within 24 hours and 89% of the cohort was able to achieve the goal P2Y12 PRU of < 194. The median P2Y12 value was 115 PRU (40, 168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients that received a DES in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

BACKGROUND:infection (CDI) in patients requiring concomitant systemic antibiotics. OBJECTIVES/OBJECTIVE:To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10-14 days), decreased CDI recurrence. METHODS:(VRE). RESULTS:= .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3-18.1). CONCLUSIONS:Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

BACKGROUND/UNASSIGNED: METHODS/UNASSIGNED:infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. RESULTS/UNASSIGNED:= .001), while treatment with carbapenem-sparing therapy was not. CONCLUSIONS/UNASSIGNED:Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort.

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.

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.

INTRODUCTION: Clostridium difficile infection (CDI) is associated with significant morbidity and mortality. Salvage therapy may include IVIG, fecal microbiota transplant (FMT) or colectomy. There is limited data regarding the effectiveness of IVIG for CDI (43-65%) or optimal dosing strategies.
METHOD(S): This is a retrospective review of critically ill patients who received IVIG (Gamunex-C) for severe or fulminant CDI at NYU Langone Health. The primary outcome was response to therapy, defined as hospital survival and complete resolution of CDI symptoms by the last day of CDI treatment without need for surgery or FMT.
RESULT(S): Fifteen patients received IVIG for severe (n=6) or fulminant (n=9) CDI, with the BI/NAP1/027 strain isolated in 27% of cases. Patients were primarily female (66%) with a median age of 62 years and had a SOFA score of 7 (IQR 4,8) at the time of IVIG administration. Twelve patients were immunosuppressed (e.g., transplant, malignancy) and nine had chronic kidney disease. There were five patients with recurrent CDI for the index infection, defined as CDI in the previous 8 weeks. Active anti-CDI therapies prior to IVIG administration included enteral vancomycin (93%), IV metronidazole (80%), rectal vancomycin (27%), fidaxomicin (7%), tigecycline (7%) and cholestyramine (7%). Median time to IVIG administration from the date of CDI positivity was 41 hours (21,75). The median total dose of IVIG administered per patient was 1.2 g/kg given over 2 days (1.5,3). Response to treatment was observed in 11 patients (73%); 4 required either colectomy (n=3) or FMT (n=1). Among the 5 patients with recurrent disease who received IVIG, response was observed in 4 cases (80%). Adverse events related to IVIG were not reported, and there were no cases of CDI recurrence within 6 months of CDI therapy completion. One in-hospital mortality was observed, which was unrelated to CDI.
CONCLUSION(S): For severe or fulminant CDI, IVIG pharmacotherapy was associated with a favorable treatment response in 73% of patients, possibly averting the need for care escalation to colectomy or FMT. Various dosing strategies were utilized, limiting assessment of a doseresponse relationship. Further data and a comparison to a cohort of critically ill patients who did not receive IVIG is needed to delineate place in therapy