Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions.

OBJECTIVE: Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes. METHODS: This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any. RESULTS: 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03). CONCLUSION: We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Concise Definitive Review for Reinitiation of Antidepressants, Antipsychotics, and Gabapentinoids in ICU Patients.

OBJECTIVE: Concise definitive review of the reinitiation of prior-to-admission neuropsychiatric medications (NPMs) in ICU patients. DATA SOURCES: Available literature on PubMed and MEDLINE databases. STUDY SELECTION: Available clinical trials and observational studies addressing the reinitiation of select NPMs (antidepressants, antipsychotics, and gabapentinoids) on various outcomes were included. DATA EXTRACTION: Eligible studies were identified by authors, and recommendations were summarized. DATA SYNTHESIS: Agitation and delirium are recognized as common complications of patients in the ICU. While there is literature that suggests patients can acutely withdraw from opioids, less data are known about withdrawal from NPM such as antidepressants, antipsychotics, and gabapentinoids. However, there is some literature that suggests reinitiating some NPMs may lead to reductions in agitation, delirium, and hospital and ICU length of stay. CONCLUSIONS: Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.

Comparison of 4F-PCC in obese and nonobese patients with life-threatening bleeding or requiring emergent surgery.

BACKGROUND: Four-factor prothrombin complex concentrate (4F-PCC) dosing is based on INR and actual body weight (ABW), with maximum doses not to exceed the dose used in patients weighing >100 kg (Kcentra PI). There are limited data comparing the efficacy of 4F-PCC between patients with low body weight ≤100 kg (LoWT) and high body weight >100 kg (HiWT). METHODS: We conducted a retrospective cohort study of patients on warfarin who received 4F-PCC for life-threatening major bleeding or requiring emergent surgery between January 2015 to June 2018 at three academic medical centers. These data were combined with a dataset from 2 randomized Phase 3b clinical trials. RESULTS: We included 388 patients who received 4F-PCC, 318 (82%) were LoWT, and 70 (18%) were HiWT. Indication for 4F-PCC for life-threatening bleeding and emergent surgery was 266 (69%) and 122 (31%) patients, respectively. The most common bleeding type was intracranial hemorrhage (41%), followed by gastrointestinal (36%). The median dose was 2283 units (25 units/kg), and 2.1% of patients required a repeat dose. CONCLUSION: In those >100 kg, we found no difference in achieving international normalized ratio (INR) ≤1.3, hemostasis in intracranial hemorrhage, or thrombosis. In-hospital mortality occurred 15% in LoWt versus 6% in HiWT (CI 1.8%-17%, p = 0.034). Achievement of INR ≤ 1.5 was significantly lower in the LoWT group compared to the HiWT group (80% versus 91%, CI -20% to -2.5%, p = 0.03).

Reliability of Field Assessment Stroke Triage for Emergency Destination Scale Use by Paramedics: Mobile Stroke Unit First-Year Experience.

Background and Purpose: Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale is a helpful tool to triage patients with stroke in the field. However, data on its reliability in the prehospital setting are lacking. We aim to test the reliability of FAST-ED scale when used by paramedics in a mobile stroke unit covering a metropolitan area. Methods: As part of standard operating mobile stroke unit procedures, paramedics initially evaluated patients. If the event characterized a stroke alert, the FAST-ED score was determined by the paramedic upon patient contact (in-person) and then independently by a vascular neurologist (VN) immediately after paramedic evaluation (remotely/telemedicine). This allowed testing of the interrater agreement of the FAST-ED scoring performance between on-site prehospital providers and remotely located VN. Results: Of a total of 238 patients transported in the first 15 months of the mobile stroke unit's activity, 173 were included in this study. Median age was 63 (interquartile range, 55.5­75) years and 52.6% were females. A final diagnosis of ischemic stroke was made in 71 (41%), transient ischemic attack in 26 (15%), intracranial hemorrhage in 15 (9%), whereas 61 (35%) patients were stroke mimics. The FAST-ED scores matched perfectly among paramedics and VN in 97 (56%) instances, while there was 0 to 1-point difference in 158 (91.3%), 0 to 2-point difference in 171 (98.8%), and 3 or more point difference in 2 (1.1%) patients. The intraclass correlation between VN and paramedic FAST-ED scores showed excellent reliability, intraclass correlation coefficient 0.94 (95% CI, 0.92­0.96; P<0.001). When VN recorded FAST-ED score ≥3, paramedics also scored FAST-ED≥3 in majority of instances (63/71 patients; 87.5%). A large vessel occlusion was identified in 16 (9.2%) patients; 13 occlusions were identified with a FAST-ED≥3 while 3 were missed. All of the latter patients had National Institutes of Health Stroke Scale score ≤5. Conclusions: We demonstrate excellent reliability of FAST-ED scale performed by paramedics when compared with VN, indicating that it can be accurately performed by paramedics in the prehospital setting.

Indications and Evidence for Dual Antiplatelet Therapy After Acute Ischemic Stroke.

The antiplatelet landscape for the secondary prevention of ischemic stroke has changed significantly over the past decade. Poststroke dual antiplatelet regimens are becoming increasingly routine as supported by recent literature and guideline recommendations. Dual antiplatelet therapy after stroke generally consists of aspirin and clopidogrel and is considered in the short term after stroke in select populations including those with mild stroke or transient ischemic attack and in patients with severe intracranial atherosclerosis. When initiating dual antiplatelet therapy, factors that may increase a patient's risk of bleeding must be weighed against the patient's risk of future ischemic events. This review focuses on antiplatelet medications available in the United States with the aim to provide a summary of the available literature on poststroke dual antiplatelet therapy, pharmacological nuances of the agents, and reversal of antiplatelets in the setting of intracerebral hemorrhage.

Collaborative Management Strategies for Drug Shortages in Neurocritical Care.

Drug shortages have become all too familiar in the health care environment, with over 200 drugs currently on shortage. In the wake of Hurricane Maria in September 2017, hospitals across the USA had to quickly and creatively adjust medication preparation and administration techniques in light of decreased availability of intravenous (IV) bags used for compounding a vast amount of medications. Amino acid preparations, essential for compounding parenteral nutrition, were also directly impacted by the hurricane. Upon realization of the impending drug shortages, hospitals resorted to alternative methods of drug administration, such as IV push routes, formulary substitutions, or alternative drug therapies in hopes of preserving the small supply of IV bags available and prioritizing them for them most critical needs. In some cases, alternative drug therapies were required, which increased the risk of medication errors due to the use of less-familiar treatment options. Clinical pharmacists rounding with medical teams provided essential, patient-specific drug regimen alternatives to help preserve a dwindling supply while ensuring use in the most critical cases. Drug shortages also frequently occur in the setting of manufacturing delays or discontinuation and drug recalls, with potential to negatively impact patient care. The seriousness of the drug shortage crisis reached public attention by December 2017, when political and pharmacy organizations called for response to the national drug shortage crisis. In this article, we review institutional mitigation strategies in response to drug shortages and discuss downstream effects of these shortages, focusing on medications commonly prescribed in neurocritical care patients.

Making a case for the right '-ase' in acute ischemic stroke: alteplase, tenecteplase, and reteplase.

INTRODUCTION: Alteplase, reteplase, and tenecteplase are tissue plasminogen activators (TPA) approved for the management of acute myocardial infarction. Only alteplase is also approved for the treatment of acute ischemic stroke (AIS). The US Food and Drug Administration has received reports of accidental administration of tenecteplase or reteplase instead of alteplase in patients with AIS, which can result in failure to treat patients with the intended agent and lead to potential overdose. AREAS COVERED: This review compares the molecular and clinical features of alteplase, reteplase, and tenecteplase (TNK), identifies factors contributing to medication errors among these agents, and provides steps to reduce medication errors. EXPERT OPINION: Primary factors contributing to medication errors among tissue plasminogen activators include the use of the abbreviations 'TPA,' 'tPA,' or 'TNK' in written or verbal orders and use of these agents in similar settings (e.g. emergency departments and critical care areas). Steps to reduce the likelihood of accidental substitution of tenecteplase or reteplase for alteplase in patients with AIS include the use of full brand or generic names and inclusion of the indication in written and verbal orders, the addition of alerts in automated dispensing machines and ordering systems and use of stroke boxes containing alteplase and materials for administration.

Risk of Hypoglycemia During Insulin Infusion Directed by Paper Protocol Versus Electronic Glycemic Management System in Critically Ill Patients at a Large Academic Medical Center.

BACKGROUND: Insulin infusions are commonly utilized to control hyperglycemia in critically ill patients and decrease hyperglycemia associated complications. Safety concerns have been raised in trials evaluating methods of glycemic control regarding the incidence of hypoglycemia and its relationship to increased mortality. Electronic glycemic management systems (eGMS) may result in less variable blood glucose (BG) control and less hypoglycemia. This study aimed to compare BG control, time in target BG range, and the rate of hypoglycemia when critically ill patients were managed with an insulin infusion guided by paper-based protocol (PBP) versus eGMS. METHODS: This retrospective review compared critically ill patients ≥ 18 years old that received insulin infusion from March to May 2015 (PBP group) and October to January 2017 (eGMS group). The primary outcome was the incidence of hypoglycemia. Secondary outcomes included frequency and severity of hypoglycemia, duration in glycemic target, length of insulin therapy, as well as ICU and hospital length of stay. RESULTS: Fifty-four patients were evaluated, 27 in each group. Percentage of days with BG <70 mg/dL was significantly reduced after eGMS implementation (21.5% v 1.3%, P < .0001) including the frequency of severe hypoglycemia (BG < 40 mg/dL) (5.4% v 0.01%, P < .0001). Patients in the eGMS group spent a greater amount of time in target BG range (31.5% v 63.7%, P < .0001). CONCLUSIONS: An eGMS has the potential to address many of the unmet needs of an optimal glycemic control strategy, minimizing hypoglycemia, and glycemic variability in a heterogeneous critically ill population.

Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients with Sepsis.

BACKGROUND: Doripenem is approved by the Food and Drug Administration for the treatment of patients with complicated intra-abdominal infections and complicated urinary tract infections. While studies have described the pharmacokinetics/pharmacodynamics (PK/PD) of doripenem in the critically ill, no study has described the probability of target attainment profile among trauma patients with sepsis. PATIENTS AND METHODS: This study was a prospective, open-label, pharmacokinetic study in the surgical intensive care unit (SICU) at Grady Health System. Thirty trauma patients with sepsis admitted to the SICU received doripenem 1 g infused over 4 hours every 8 hours for three doses. Blood samples were taken just before and after the third dose. A two-compartment model was fit to the data using non-parametric population PK modeling software. Embedded with the final PK model, a Monte Carlo Simulations (MCS) was performed to determine the PK/PD profile of doripenem 1 g, infused over 4 hours, every 8 hours after administration of the first and fourth doses. RESULTS: Overall, the model fit the data well, and mean (standard deviation) clearance and volume of the central compartment were 16.9 (11.4) L/h and 28.5 (16.0) L, respectively. In the MCS analyses, doripenem 1 g, infused over 4 hours, administered every 8 hours, conferred >90% probabilities of achieving 30-50% time greater than the minimum inhibitory concentration (30-50% T>MIC) for MICs ≤2 mg/L after infusion of both the first and fourth doses. The MCS indicated that more intensive doripenem dosing schemes should be considered for organisms with MIC values in excess of 2 mg/L. CONCLUSIONS: This is the first study to describe the doripenem PK/PD in critically ill patients with trauma. Among these patients, the MCS analyses suggest that current dosing strategies may be ineffective when the MIC value for the infecting pathogen is expected to be above 2 mg/L.

A review of current agents for anticoagulation for the critical care practitioner.

There has been a tremendous boom in the arena of anticoagulant therapy recently. Although the indications for these agents reside in the noncritical care environment, over time, the impact of these agents have infiltrated the critical care environment particularly due to devastating complications with associated use. With so many newer agents on the market or coming down the pipeline, it is easy to become overwhelmed. It is important that the critical care practitioner does not ignore these agents but becomes familiar with them to better prepare for the management of patients on one or more anticoagulant agents in the intensive care unit. To equip the critical care practitioners with the knowledge about commonly used anticoagulants, we provide an extensive review of the pharmacology, indications, and adverse effects related to these agents as well as suggestions on preventing or managing complications.