Postintubation Sedation Practices Within Multiple Emergency Departments Across a Large Pediatric Health Care Organization.

OBJECTIVE: Children requiring rapid or standard sequence intubation are at risk of experiencing paralysis without adequate sedation when the duration of neuromuscular blockade exceeds the duration of sedation provided by the induction agent. The objective of this study was to evaluate the rate of appropriately timed postintubation sedation (PIS; defined as the administration of PIS before the clinical effects of the induction agent have dissipated) in patients requiring intubation across multiple emergency department/urgent care sites within a large pediatric health care organization. METHODS: This retrospective cohort study included patients admitted to 1 of 6 affiliated pediatric emergency department or urgent care sites who were intubated with an induction agent and neuromuscular blocker between January 2016 and December 2021. Patients were excluded if they were intubated in the setting of status epilepticus or cardiac arrest. Stepwise logistic regression identified factors associated with appropriately timed PIS. RESULTS: A total of 283 patients met the inclusion criteria (mean age, 8 ± 7.6 years; 56% male). Two hundred thirty-eight patients (83%) received some form of PIS (105 [37%] received appropriately timed PIS and 133 [47%] received delayed PIS), and 45 patients (16%) received no PIS. The median time to receive PIS following administration of the induction agent was 21 minutes (interquartile range, 11-40 minutes). Patients induced with fentanyl were the least likely to receive PIS, whereas patients induced with etomidate were the most likely. However, because of the short duration of etomidate, most patients induced with etomidate failed to receive PIS in a timely manner. CONCLUSIONS: Delayed PIS is common and may result in periods of ongoing paralysis without adequate sedation. Emergency department providers and pharmacists must recognize the brevity of some induction agents and provide more timely PIS.

Emergency medicine pharmacist interventions reducing exposure to costs (EMPIRE-C).

INTRODUCTION: Emergency Medicine (EM) pharmacists are considered essential healthcare providers in the Emergency Department (ED). Limited data are available representing the types of interventions performed by ED pharmacists, especially in community-based health systems. METHODS: Retrospective, multi-centered, observational review of documented EM clinical pharmacist interventions into the electronic medical record (EMR) across five separate EDs between July 1, 2020 and June 30, 2021. Interventions were separated into three categories: ED Intervention, ED Outpatient Culture Review, and ED Discharge Antimicrobial Review. Interventions with supporting literature related to cost avoidance were also analyzed. RESULTS: A total of 23,794 interventions were logged by the EM pharmacy team between the three categories. Of those, 9181 were cost avoidance interventions resulting in $5,350,755.63 in total cost avoidance, or $582.81 per intervention. CONCLUSION: EM pharmacists practicing in community settings have a substantial impact on patients as evidenced by the large quantity and variety of interventions logged which also results in significant cost avoidance to the healthcare system.

Comparison of 3 Different Prothrombin Complex Concentrate Regimens for Emergent Warfarin Reversal: PCCWaR Study.

BACKGROUND: The ideal dose and specific prothrombin complex concentrate (PCC) for warfarin reversal is unknown. OBJECTIVE: To evaluate the reduction in international normalized ratio (INR) of 3 different PCC dosing regimens: fixed-dose activated 4-factor PCC (aPCC), fixed-dose 4-factor PCC (4PCC), and standard-dose 4PCC. METHODS: This was a multicenter retrospective cohort review. Patients >18 years of age who received PCC for warfarin reversal between January 1, 2017, and December 31, 2017, were screened for inclusion. Patients were excluded if they did not receive the correct PCC dosing regimen, received PCC for nonwarfarin bleeding, had a baseline INR less than 2, or received a massive transfusion protocol. Two institutions utilized aPCC dosed at 500 IU for INR <5 and 1000 IU for INR ≥5. Two institutions utilized fixed-dose 4PCC at 1500 to 2000 units depending on patient factors. Two institutions utilized 4PCC package insert dosing. The primary outcome was achievement of post-PCC target INR ≤1.4. Secondary outcomes included percentage change in INR, lowest 24-hour INR, and mortality. RESULTS: A total of 154 patients were included (fixed-dose aPCC: n = 29; fixed-dose 4PCC: n = 53; standard-dose 4PCC: n = 72). There was no statistical difference between groups in achieving the primary outcome (58.6% vs 69.8% vs 79.2%, respectively; P = 0.103) or any secondary outcomes. CONCLUSION AND RELEVANCE: There was no difference in the ability to achieve a post-PCC INR of ≤1.4 between 3 different PCC regimens for warfarin reversal. Additional research is warranted to determine the ideal dose and PCC agent for warfarin reversal.

Fixed-dose prothrombin complex concentrate for emergent warfarin reversal among patients with intracranial hemorrhage.

INTRODUCTION: Four-factor prothrombin complex concentrate (4PCC) is the preferred reversal agent for warfarin reversal, although the ideal dose is unknown. Fixed-dose 4PCC offers simplified dosing compared to standard-dosing algorithms with potentially lower risks of thromboembolic complications given lower doses are typically utilized. METHODS: Retrospective, observational, multicentered, pre- post- study of patients who received 4PCC for warfarin reversal among four hospitals within the same regional health system. Standard-dose patients received variable doses ranging from 25 to 50 units/kg based on total body weight and initial INR and fixed-dose patients received 2000 units. The primary outcome was achievement of a target INR ≤ 1.4 on the first post-4PCC INR result. RESULTS: After exclusions, 48 and 42 patients were analyzed in the standard-dose and fixed-dose groups, respectively. There was no difference in the ability to achieve a target INR of ≤1.4 (82.6% vs 81.5%, p = 0.14). Both groups received the same median dose of 2000 units, although fixed-dose patients actually received a higher weight-based dose than standard-dose patients (27 units/kg vs 24.5 units/kg). CONCLUSION: A fixed-dose 4PCC regimen of 2000 units among patients with ICH was as effective as standard-dose 4PCC for INR reversal among patients with ICH. However, fixed-doses of 2000 units at times exceeded standard 4PCC doses which may be contradictory to the goals of fixed-dose 4PCC for warfarin reversal.

Time to antibiotic administration: Sepsis alerts called in emergency department versus in the field via emergency medical services.

INTRODUCTION: The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) identifies patients with "severe sepsis" and mandates antibiotics within a specific time window. Rapid time to administration of antibiotics may improve patient outcomes. The goal of this investigation was to compare time to antibiotic administration when sepsis alerts are called in the emergency department (ED) with those called in the field by emergency medical services (EMS). METHODS: This was a multi-center, retrospective review of patients designated as sepsis alerts in ED or via EMS in the field, presenting to four community emergency departments over a six-month period. RESULTS: 507 patients were included, 419 in the ED alert group and 88 in the field alert group. Mean time to antibiotic administration was significantly faster in the field alert group when compared to the ED alert group (48.5 min vs 64.5 min, p < 0.001). Patients were more likely to receive antibiotics within 60 min of ED arrival in the field alert group (59.1% vs 44%, p = 0.01). Secondary outcomes including mortality, hospital length of stay, intensive care unit length of stay, sepsis diagnosis on admission, Clostridioides difficile infection rates, fluid bolus utilization, anti-MRSA antibiotic utilization rates, and anti-Pseudomonal antibiotic utilization rates were not found to be significantly different. CONCLUSIONS: Sepsis alerts called in the field via EMS may decrease time to antibiotics and increase the likelihood of antibiotic administration occurring within 60 min of arrival when compared to those called in the ED.

Emergent Warfarin Reversal With Fixed-Dose 4-Factor Prothrombin Complex Concentrate.

BACKGROUND: Four-factor prothrombin complex concentrate (4FPCC) is used for emergent warfarin reversal, but dosing remains controversial. Following approval, further studies have evaluated a variety of fixed-dose regimens. The studies utilized lower doses as compared with package insert dosing and provided data in regard to efficacy, safety, and cost savings. Further data are needed, however, to determine which fixed-dose regimen provides optimal efficacy and safety for emergent warfarin reversal. OBJECTIVES: The purpose of this study is to evaluate the efficacy, safety, and cost-savings of a fixed-dose 4FPCC protocol. METHODS: This multicentered, retrospective chart review of adult patients requiring 4FPCC for emergent warfarin reversal utilized a fixed-dose regimen of 1500 units. The 2 primary outcomes were the proportion of patients who achieved a post-4FPCC international normalized ratio (INR) of ≤1.5 and ≤2. Secondary outcomes included thrombotic events within 7 days of 4FPCC administration and survival to discharge. A cost analysis was also performed to identify potential cost savings. RESULTS: Of the 64 patients included, 44 (68.8%) achieved a post-4FPCC INR ≤1.5, and 61 (95.3%) achieved a post-4FPCC INR ≤2.0. No thrombotic events were reported; 55 (85.9%) patients survived to hospital discharge. More than $1000 was saved per patient via utilization of the fixed-dose protocol. CONCLUSION AND RELEVANCE: A fixed-dose of 1500 units of 4FPCC successfully achieved a target INR of ≤1.5 in the majority of patients and resulted in no thrombotic events. This study adds to the data evaluating alternative 4FPCC dosing regimens in comparison to package insert recommended dosing.

Multi-centered evaluation of a novel fixed-dose four-factor prothrombin complex concentrate protocol for warfarin reversal.

INTRODUCTION: Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal. METHODS: This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications. RESULTS: A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC. CONCLUSION: A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal.

OBJECTIVES: To compare the international normalized ratio normalization efficacy of activated prothrombin complex concentrates and 4-factor prothrombin complex concentrates and to evaluate the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage. DESIGN: Retrospective, Multicenter Cohort. SETTING: Large, Community, Teaching Hospital. PATIENTS: Patients greater than 18 years old and received either activated prothrombin complex concentrate or 4-factor prothrombin complex concentrate for the treatment of warfarin-associated hemorrhage. We excluded those patients who received either agent for an indication other than warfarin-associated hemorrhage, pregnant, had a baseline international normalized ratio of less than 2, received a massive transfusion as defined by hospital protocol, received plasma for treatment of warfarin-associated hemorrhage, or were treated for an acute warfarin ingestion. INTERVENTIONS: Patients in the activated prothrombin complex concentrate group (enrolled from one hospital) with an international normalized ratio of less than 5 received 500 IU and those with an international normalized ratio greater than 5 received 1,000 IU. Patients in the 4-factor prothrombin complex concentrate (enrolled from a separate hospital) group received the Food and Drug Administration approved dosing algorithm. MEASUREMENTS AND MAIN RESULTS: A total of 158 patients were included in the final analysis (activated prothrombin complex concentrate = 118; 4-factor prothrombin complex concentrate = 40). Those in the 4-factor prothrombin complex concentrate group had a higher pretreatment international normalized ratio (2.7 ± 1.8 vs 3.5 ± 2.9; p = 0.0164). However, the posttreatment international normalized ratio was similar between the groups. In addition, even when controlling for differences in the pretreatment international normalized ratio, there was no difference in the ability to achieve a posttreatment international normalized ratio of less than 1.4 (odds ratio, 0.753 [95% CI, 0.637-0.890]; p = 0.0009). Those in the activated prothrombin complex concentrate group did have higher odds of achieving a posttreatment international normalized ratio of less than 1.2 (odds ratio, 3.23 [95% CI, 1.34-7.81]; p = 0.0088). There was only one posttreatment thrombotic complication reported. CONCLUSIONS: A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events.

Wafer-Scale Full-Coverage Self-Limiting Assembly of Particles on Flexible Substrates.

Self-limiting assembly of particles represents the state-of-the-art controllability in nanomanufacturing processes where the assembly stops at a designated stage, providing a desirable platform for applications requiring delicate thickness control such as optics, electronics, and catalytic systems. Most successes in self-limiting assembly are limited to self-assembled monolayers (SAMs) of small molecules on inorganic, chemically homogeneous rigid substrates (e.g., Au and SiO2) through surface-interaction mechanisms. Similar mechanisms, however, cannot achieve a uniform assembly of particles on flexible polymer substrates. The complex configurations and conformations of polymer chains create a surface with nonuniform distributions of chemical groups and phases. In addition, most assembly mechanisms require good solvent wettability, where many desirable but hard-to-wet particles and polymer substrates are excluded. Here, we demonstrate a collision-based self-limiting assembly (CSA) to achieve wafer-scale, full-coverage, close-packed monolayers of hydrophobic particles on hydrophobic polymer substrates in aqueous solutions. The kinetic assembly and self-limiting processes are facilitated and controlled by the combined acoustic and shear fields. We envision many applications in functional coatings and showcase their feasibility in structural coloration. Importantly, such functional coatings can be repaired using CSA, and both particles and polymer substrate can be recycled.

Anisotropic band flattening in graphene with one-dimensional superlattices.

Patterning graphene with a spatially periodic potential provides a powerful means to modify its electronic properties1-3. In particular, in twisted bilayers, coupling to the resulting moiré superlattice yields an isolated flat band that hosts correlated many-body phases4,5. However, both the symmetry and strength of the effective moiré potential are constrained by the constituent crystals, limiting its tunability. Here, we have exploited the technique of dielectric patterning6 to subject graphene to a one-dimensional electrostatic superlattice (SL)1. We observed the emergence of multiple Dirac cones and found evidence that with increasing SL potential the main and satellite Dirac cones are sequentially flattened in the direction parallel to the SL basis vector, behaviour resulting from the interaction between the one-dimensional SL electric potential and the massless Dirac fermions hosted by graphene. Our results demonstrate the ability to induce tunable anisotropy in high-mobility two-dimensional materials, a long-desired property for novel electronic and optical applications7,8. Moreover, these findings offer a new approach to engineering flat energy bands where electron interactions can lead to emergent properties9.

Urinary tract infection pocket card effect on preferred antimicrobial prescribing for cystitis among patients discharged from the emergency department.

PURPOSE: To evaluate the impact of a urinary tract infection (UTI) pocket card on preferred antibiotic prescribing for patients discharged from the emergency department (ED) with a diagnosis of cystitis. METHODS: A multicenter, retrospective, pre-post study was conducted to compare outcomes following the introduction of a UTI pocket card. The primary outcome was prescribing rates for institutional first-line preferred antibiotics (cephalexin and nitrofurantoin) versus other antimicrobials for cystitis. Secondary outcomes included prescriber adherence to recommended therapy in regards to discharge dose, frequency, duration, and healthcare utilization rates. RESULTS: The study included 915 patients in total, 407 in the preintervention group and 508 in the postintervention group. The frequency of preferred antibiotic prescribing was significantly increased after the introduction of a UTI pocket card compared to prior to its introduction (81.7% vs 72.0%, P = 0.001). Significant increases in prescribing of an appropriate antibiotic dose (78.0% vs 66.8%, P < 0.0001) and frequency (64.2% vs 47.4%, P < 0.0001) were also found post intervention. No significant differences were seen between the pre- and postintervention groups with regards to healthcare utilization rates. CONCLUSION: A UTI pocket card increased preferred antibiotic prescribing for cystitis in the ED. This study provides data on a successful antimicrobial stewardship intervention in the ED setting.

Analysis of anticoagulation reversal survey (ARES).

OBJECTIVES: Despite the availability of FDA-labeled anticoagulant reversal agents, there is considerable variability in clinical practice as to the regimen and agent used for reversal. The objective of this study was to characterize the current practices of pharmacists surrounding the reversal of anticoagulant-associated life-threatening hemorrhage. Methods: A cross-sectional analysis of critical care and emergency medicine pharmacists. Current practice was compared for the type of hospital, country region, and type of ordering physician. In addition, pharmacists were asked to rank their involvement with activities involved with the reversal of anticoagulants. Respondents ranked their involvement with these activities as either never involved, rarely involved, occasionally involved, frequently involved, or always involved. Results:281 respondents were included. The majority used 4-factor PCC for warfarin reversal (92.9%) and factor Xa inhibitor reversal (79.7%). However, only 58.7% used the labeled dose of 4-PCC for warfarin reversal. Of the 30.6% that utilized a fixed-dose regimen, the most common regimen was 1500 units once. A higher proportion of respondents practicing in a teaching hospital reported that they used activated prothrombin complex concentrates for reversal of factor Xa inhibitor (22 [12.2%] vs. 5 [5%]; p < 0.05) or coagulation factor Xa (recombinant)-inactivated-zhzo (31 [17.2%] vs. 5 [5%]; p < 0.05). In addition, the majority of respondents utilized idarucizumab for dabigatran reversal. The only involvement activity in which <50% of respondents said they were frequently involved or always involved was 'administration of reversal agent.' Conclusions: There is considerable variability in which agents were utilized for anticoagulant-associated bleeding reversal.

Hemodynamic Effects of Propofol for Induction of Rapid Sequence Intubation in Traumatically Injured Patients.

Present guidelines for emergency intubation in traumatically injured patients recommend rapid sequence intubation (RSI) as the preferred method of airway management but specific pharmacologic agents for RSI remain controversial. To evaluate hemodynamic differences between propofol and other induction agents when used for RSI in trauma patients. Single-center, retrospective review of trauma patients intubated in the emergency department. Patients were divided in two groups based on induction agent, propofol or nonpropofol. The primary outcome was incidence of hypotension within 30 minutes of intubation. Secondary outcomes included hospital length of stay and inhospital mortality. The study protocol was approved by the Institutional Review Board. Of the 744 patients identified, 83 were analyzed, 43 in the propofol group and 40 in the nonpropofol group. Groups were similar at baseline in terms of pre-RSI hemodynamics, injury mechanism, initial Glasgow Coma Score, and Injury Severity Score. On univariate analysis, although not statistically significant, postintubation hypotension was more common in patients who received propofol compared with those who did not, 39.5 per cent versus 22.5 per cent (P = 0.9). When adjusted for age, Injury Severity Score, and pre-RSI hemodynamics, the risk of hypotension among propofol-treated patients was significantly higher (OR = 3.64; 95% Confidence interval 1.16-13.24). There were no significant differences between groups in hospital length of stay or mortality. Propofol increases the odds of postintubation hypotension in traumatically injured patients. Considerable caution should be used when contemplating the use of propofol the for induction of injured patients requiring RSI because other agents possess more favorable hemodynamic profiles.