Guidelines for Neuroprognostication in Critically Ill Adults with Moderate-Severe Traumatic Brain Injury.

BACKGROUND: Moderate-severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted. RESULTS: After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining "poor" functional outcomes. For consistency, we treated "poor" as "unfavorable". Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using "moderately reliable" predictors or prediction models, the clinician must acknowledge "substantial" uncertainty in the prognosis. CONCLUSIONS: These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication.

Guidelines for neuroprognostication in adults with traumatic spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (tSCI) impacts patients and their families acutely and often for the long term. The ability of clinicians to share prognostic information about mortality and functional outcomes allows patients and their surrogates to engage in decision-making and plan for the future. These guidelines provide recommendations on the reliability of acute-phase clinical predictors to inform neuroprognostication and guide clinicians in counseling adult patients with tSCI or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of an appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Timing/Setting question was framed as "When counseling patients or surrogates of critically ill patients with traumatic spinal cord injury, should < predictor, with time of assessment if appropriate > be considered a reliable predictor of < outcome, with time frame of assessment >?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four Grading of Recommendations Assessment, Development, and Evaluation criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. Good practice recommendations addressed essential principles of neuroprognostication that could not be framed in the Population/Intervention/Comparator/Outcome/Timing/Setting format. Throughout the guideline development process, an individual living with tSCI provided perspective on patient-centered priorities. RESULTS: Six candidate clinical variables and one prediction model were selected. Out of 11,132 articles screened, 369 met inclusion criteria for full-text review and 35 articles met eligibility criteria to guide recommendations. We recommend pathologic findings on magnetic resonance imaging, neurological level of injury, and severity of injury as moderately reliable predictors of American Spinal Cord Injury Impairment Scale improvement and the Dutch Clinical Prediction Rule as a moderately reliable prediction model of independent ambulation at 1 year after injury. No other reliable or moderately reliable predictors of mortality or functional outcome were identified. Good practice recommendations include considering the complete clinical condition as opposed to a single variable and communicating the challenges of likely functional deficits as well as potential for improvement and for long-term quality of life with SCI-related deficits to patients and surrogates. CONCLUSIONS: These guidelines provide recommendations about the reliability of acute-phase predictors of mortality, functional outcome, American Spinal Injury Association Impairment Scale grade conversion, and recovery of independent ambulation for consideration when counseling patients with tSCI or their surrogates and suggest broad principles of neuroprognostication in this context.

Post-discharge venous thromboembolism prophylaxis in hospitalized trauma patients: A retrospective comparison of patients receiving versus not receiving post-discharge prophylaxis.

BACKGROUND: Risk of venous thromboembolism (VTE) in many trauma patients extends beyond hospitalization, but there is a paucity of evidence to guide the use of post-discharge prophylaxis (PDP). METHODS: A retrospective cohort study of trauma patients deemed moderate-to-high risk for VTE (risk assessment profile score [RAP] ≥5) who were prescribed PDP based on an internal clinical guideline assessing injury pattern and mobility status. PDP patients were compared with those that did not receive post-discharge prophylaxis (NPDP). RESULTS: 1512 patients were included. PDP group had higher mean RAP score (7.3 vs. 6.4, p â€‹< â€‹0.001), more likely to have a complex orthopedic fracture and underwent a longer median hospital (4.7 vs. 2.9 days, p â€‹< â€‹0.001). No difference between groups in 90-day VTE (11 [1.5 â€‹%] (PDP) vs. 8 [1.0 â€‹%] (NPDP), p â€‹= â€‹0.50), clinically relevant bleeding (p â€‹= â€‹0.58), or readmission (p â€‹= â€‹0.46). CONCLUSIONS: VTE incidence, clinically relevant bleeding, and readmission 90-days after hospital discharge were low and similar between PDP and NPDP groups. PDP prescribed in a presumably higher VTE risk trauma population may mitigate the long-term risk of VTE.

Guidelines for Neuroprognostication in Critically Ill Adults with Intracerebral Hemorrhage.

BACKGROUND: The objective of this document is to provide recommendations on the formal reliability of major clinical predictors often associated with intracerebral hemorrhage (ICH) neuroprognostication. METHODS: A narrative systematic review was completed using the Grading of Recommendations Assessment, Development, and Evaluation methodology and the Population, Intervention, Comparator, Outcome, Timing, Setting questions. Predictors, which included both individual clinical variables and prediction models, were selected based on clinical relevance and attention in the literature. Following construction of the evidence profile and summary of findings, recommendations were based on Grading of Recommendations Assessment, Development, and Evaluation criteria. Good practice statements addressed essential principles of neuroprognostication that could not be framed in the Population, Intervention, Comparator, Outcome, Timing, Setting format. RESULTS: Six candidate clinical variables and two clinical grading scales (the original ICH score and maximally treated ICH score) were selected for recommendation creation. A total of 347 articles out of 10,751 articles screened met our eligibility criteria. Consensus statements of good practice included deferring neuroprognostication-aside from the most clinically devastated patients-for at least the first 48-72 h of intensive care unit admission; understanding what outcomes would have been most valued by the patient; and counseling of patients and surrogates whose ultimate neurological recovery may occur over a variable period of time. Although many clinical variables and grading scales are associated with ICH poor outcome, no clinical variable alone or sole clinical grading scale was suggested by the panel as currently being reliable by itself for use in counseling patients with ICH and their surrogates, regarding functional outcome at 3 months and beyond or 30-day mortality. CONCLUSIONS: These guidelines provide recommendations on the formal reliability of predictors of poor outcome in the context of counseling patients with ICH and surrogates and suggest broad principles of neuroprognostication. Clinicians formulating their judgments of prognosis for patients with ICH should avoid anchoring bias based solely on any one clinical variable or published clinical grading scale.

Impact of a Multifaceted Intervention on Antibiotic Prescribing for Cystitis and Asymptomatic Bacteriuria in 23 Community Hospital Emergency Departments.

Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.

Guidelines for Neuroprognostication in Adults with Guillain-Barré Syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10-30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: "When counseling patients or surrogates of critically ill patients with Guillain-Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed.

Guidelines for Neuroprognostication in Comatose Adult Survivors of Cardiac Arrest.

BACKGROUND: Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: "When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?" Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence.

Implementation and Impact of Critical Care Pharmacist Addition to a Telecritical Care Network.

Critical care pharmacists when incorporated into the ICU team, have been shown to improve outcomes in critically ill patients by decreasing mortality, improving morbidity and reducing cost. As telehealth continues to evolve, the incorporation of a critical care pharmacist into a comprehensive telecritical care (TCC) service will allow increased comprehensive pharmacotherapeutic care for those in smaller, community or rural hospitals. OBJECTIVES: To describe the implementation of a TCC pharmacist into an established TCC network, classify interventions performed, and quantify cost avoidance generated through pharmacist interventions. DESIGN: Multicenter, observational cohort study and retrospective return on investment, performed between December 2019 and December 2021. SETTING AND PARTICIPANTS: Critically ill adult patients, admitted to an ICU located in any of our eight community hospitals (50 ICU beds) within a large, 25-hospital integrated healthcare system (563 ICU beds total) in the United States. MAIN OUTCOMES AND MEASURES: The TCC pharmacist service was implemented in 8-hour shifts, initially available 5 days per week, then expanded to 7 days per week. Critical care pharmacist interventions were categorized by clinical type established utilizing American Society of Health-System Pharmacists benchmarking standards and the latest cost avoidance data. RESULTS: During the 2-year analysis period, TCC pharmacists documented 2,838 interventions generating $1,664,254 of gross cost avoidance and a return on investment of 4.5:1. CONCLUSIONS AND RELEVANCE: It is feasible to implement a TCC pharmacist within an established TCC network. Our experience showed enhanced comprehensive care of critically ill patients located in community hospitals within a large, integrated healthcare system, demonstrated significant cost avoidance, and has led to other initiatives, including a collaborative clinical/operational partnership with Life Flight.

Order Substitutions and Education for Balanced Crystalloid Solution Use in an Integrated Health Care System and Association With Major Adverse Kidney Events.

Importance: Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids. Objective: To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system. Design, Setting, and Participants: This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution. Exposures: Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline. Main Outcomes and Measures: The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days. Results: Among 148 423 patients (median [IQR] age, 47 [30-67] years; 91 302 women [61%]), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio [OR], 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32). Conclusions and Relevance: In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.

Variables associated with adequate INR reversal in warfarin treated patients receiving 4-factor prothrombin complex concentrate.

Dosing of 4-factor prothrombin complex concentrate (4FPCC) in warfarin treated patients generally utilizes international normalized ratio (INR) and patient weight. The recommended maximum dosing for all INR categories is capped at 100 kg weight. Whether this affects INR reversal is unknown. Furthermore, characteristics associated with adequate INR reversal need to be further elucidated. This was a multi-center, retrospective cohort study of 186 patients who received 4FPCC for INR reversal in the setting of warfarin-associated hemorrhage or need for emergent INR reversal. Utilizing multiple regression analysis, we evaluated INR reversal, achievement of hemostasis, and 28-day all-cause mortality. A target INR < 1.4 was achieved in 132 of 186 patients (71%). Factors significantly affecting the odds of achieving target INR were age in years (OR 1.03; 95% CI 1.01-1.06; P = 0.01), weight-based 4FPCC dose (units/kg) (OR 1.04; 95% CI 1.00-1.08; P = 0.03), and 4FPCC dosing normalized to INR (units/kg/INR) (OR 1.18; 95% CI 1.03-1.35; P = 0.02). Hemostasis was achieved in 109 of 148 bleeding patients (73.6%). Blood transfusions were associated with not achieving hemostasis (OR 0.44; 95% CI 0.21-0.93; P = 0.03). All-cause 28-day mortality was 21.5% and was associated with intracranial hemorrhage (OR 2.83; 95% CI 1.38-5.8; P = 0.01). Adequate INR reversal was associated with age, weight-based 4FPCC dose, and dosing normalized to INR (units/kg/INR). Future studies should evaluate the appropriateness of current INR targets for warfarin reversal and alternative 4FPCC dosing strategies such as utilizing a 4FPCC dosing ratio of units/kg/INR.

High-dose versus low-dose 4-factor prothrombin complex concentrate for factor Xa inhibitor reversal in intracranial hemorrhage.

BACKGROUND & PURPOSE: 4-factor prothrombin complex concentrate (4FPCC) is used off-label for factor Xa (FXa) inhibitor-associated intracranial hemorrhage (ICH). Guideline recommendations provide various 4FPCC dosing regimens for FXa inhibitor reversal in this setting. We evaluated 4FPCC weight-based dosing and outcomes in FXa inhibitor-associated ICH. METHODS: We conducted a multi-center, retrospective, cohort study of ICH patients between July 2017 and February 2020. Patients were greater than 18 years of age, received 4FPCC, and were taking apixaban, rivaroxaban, or edoxaban. Patients were separated into high- (≥35 units/kg) or low-dose (<35 units/kg) 4FPCC groups. The primary outcome was hemostasis achievement. Secondary outcomes included in-hospital mortality, intensive care unit and hospital length of stay, discharge disposition, and thrombotic events. Outcomes were evaluated with binary logistic regression. RESULTS: Of 390 patients identified, 89 were included with 74 and 15 in the high- vs low-dose groups, respectively. Mean (SD) age was 76.6 (±10.8) years. Most were taking a FXa inhibitor for atrial fibrillation (76.4%) and apixaban was the most common FXa inhibitor (65.2%). Hemostasis achievement was greater in the high- vs low-dose group (89.2% vs 46.7%; OR 11.2; 95% CI 2.4-52.6, P = 0.002). Thrombotic events were 8.2% and 6.7% in the high vs low-dose groups, respectively (OR 0.8; 95% CI 0.08-8.2, P = 0.87). No statistically significant differences were found in secondary outcomes. CONCLUSION: In patients with FXa inhibitor-associated ICH, high-dose 4FPCC was associated with increased odds of hemostasis achievement. There was no difference in thrombotic events.

Melatonin, Ramelteon, Suvorexant, and Dexmedetomidine to Promote Sleep and Prevent Delirium in Critically Ill Patients: A Narrative Review With Practical Applications.

Sleep plays an important role in the recovery of critically ill patients. However, patients in the intensive care unit (ICU) often suffer sleep disturbances and abnormal circadian rhythms, which may increase delirium and lengthen ICU stay. Nonpharmacologic strategies for preventing and treating sleep disturbances and delirium, such as overnight eye masks and ear plugs, are usually employed first, given the lack of adverse effects. However, a multimodal approach to care including pharmacotherapy may be necessary. Despite the limited available data supporting their use, medications such as melatonin, ramelteon, suvorexant, and dexmedetomidine may promote sleep and improve a variety of patient-centric outcomes such as delirium. This narrative review focuses on these nonbenzodiazepine agents used for sleep in the ICU. Practical application of each of these agents is described for when providers choose to utilize one of these pharmacotherapies to promote sleep or prevent delirium.

COVID-19 preparedness: Clinical pharmacy services remote staffing in a quaternary, level I trauma and comprehensive stroke center.

PURPOSE: The rapid spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has strained the resources of healthcare systems around the world. In accordance with recommendations from the World Health Organization, Centers for Disease Control and Prevention, and US Department of Defense, Intermountain Medical Center (IMED) in Murray, UT, has developed a plan to provide remote clinical pharmacy services to protect the health of pharmacy caregivers while maintaining appropriate clinical pharmacy coverage to optimally care for patients. SUMMARY: The utilization of telemedicine technology permits clinical pharmacists to readily communicate with nurses, physicians, other caregivers, and patients. We have identified strategies to allow clinical pharmacists to continue to participate in daily rounds, provide consultations under collaborative practice agreements, verify medication orders, collect medication histories, provide antimicrobial stewardship, and deliver medication education to patients from off-site locations. The pharmacy department at IMED proactively tested telemedicine technologies, defined the roles of clinical pharmacists, and identified communication strategies prior to a rapid rise in COVID-19 cases in the state of Utah. CONCLUSION: The proactive measures described can help ensure that pharmacy caregivers have appropriate remote access and are capable of confidently using the resources. These steps allow for optimal care of hospitalized patients and promote social distancing, which may have the added benefit of decreasing the spread of SARS-CoV-2 among patients and caregivers.

Alteplase Therapy for Acute Ischemic Stroke in Pregnancy: Two Case Reports and a Systematic Review of the Literature.

Acute ischemic stroke (AIS) during pregnancy is a rare but serious complication. Intravenous alteplase is the only medication approved for hyperacute treatment of AIS; however, it has not been evaluated prospectively in pregnancy. Pregnancy was an exclusion criterion in prospective AIS studies and was only recently removed as a relative contraindication in the 2018 American Heart Association/American Stroke Association Stroke guidelines. Due to the exclusion of pregnant women from randomized controlled trials, the safety of fibrinolytic therapy in pregnant patients is not well established. In this review, we report the use of intravenous alteplase for AIS in two pregnant patients, with temporally associated clinical improvement and without complications to either the mother or fetus. Additionally, we summarize a systematic review of the literature for both intravenous and intra-arterial alteplase use for AIS in pregnant patients. A total of 31 cases met inclusion criteria for this review of assessment of safety and efficacy of alteplase use in pregnancy. Existing case reports and guidelines support the use of alteplase for AIS in pregnant patients without contraindications.

Comparative thrombosis risk of vascular access devices among critically ill medical patients.

BACKGROUND: Central venous catheters (CVC) and peripherally inserted central catheters (PICCs) are central vascular access devices (CVADs) that facilitate administration of medications among critically ill patients. Both are associated with risk of venous thromboembolism (VTE). The relative risk of VTE between these catheter types is not well defined. We report the rate of VTE in intensive care unit (ICU) medical patients receiving PICC, CVC, both, or neither. METHODS: We conducted a single-center, retrospective cohort study of medical-ICU patients between November 2007 and November 2013 grouped by receipt of CVC, PICC, both, or neither. The primary outcome was the rate of 30-day symptomatic venous thrombosis (upper and lower deep vein thrombosis and pulmonary embolism). Cox modeling was used to analyze this population and adjust for comorbidities which could contribute to VTE. Secondary outcomes included VTE location, major bleeding, and all-cause mortality among patients with and without CVADs. RESULTS: We analyzed 5788 patients. CVADs were placed in 2403 (42%) patients (PICC, n = 816; CVC, n = 1153; both, n = 434). Compared with no CVAD, the hazard ratio (HR) for 30-day VTE was 1.81 (95% CI 1.52-2.17) for any CVAD, 1.90 (95% CI 1.52-2.37) for PICC, 1.57 (95% CI 1.26-1.96) for CVC, and 2.70 (95% CI 2.09-3.47) for both. PICCs had a non-significantly higher HR for VTE compared with CVC (1.21; 95% CI 0.94-1.55). For patients with both a CVC and PICC the HR for VTE was 1.72 times that of solitary CVAD (95% CI 1.32-2.23). CONCLUSIONS: Among critically ill medical patients, PICCs and CVCs were associated with increased risk of VTE. Placement of both conferred higher risk of VTE compared with either alone.

Newly Initiated In-Hospital Antipsychotics Continued at Discharge in Non-psychiatric Patients.

Objectives: Antipsychotics are commonly initiated in the hospital for agitation and delirium and may be inappropriately continued upon floor transfer and at discharge. We sought to evaluate the magnitude of this issue within our health care system. Methods: We conducted a multicenter, retrospective cohort study within a 22-hospital health care system to evaluate the proportion of patients without identifiable psychiatric illness who received newly initiated inpatient antipsychotics and were then continued on an antipsychotic at hospital discharge. Results: Of 23 049 patients who received at least 1 in-hospital dose of haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone, 8297 patients were included in the final analysis after applying exclusion for identifiable psychiatric illness or previous antipsychotic use. Ultimately, 334 patients (4%) were discharged with a new antipsychotic prescription. Patients receiving antipsychotics at discharge were more likely as an inpatient to receive quetiapine (77.2% vs 35.9%; odds ratio [OR]: 6.1, 95% confidence interval [CI]: 4.7-8.0; P < .001) and less likely to receive haloperidol (15% vs 47%; OR: 0.2, 95% CI: 0.14-0.27; P < .001) or olanzapine (16.2% vs 20.9%; OR: 0.73, 95% CI: 0.53-0.98; P < .04). Conclusions: Antipsychotics may be inappropriately continued in non-psychiatric patients at hospital discharge. Strategies to limit potentially unnecessary antipsychotics upon discharge should be evaluated.

Three-Factor Versus Four-Factor Prothrombin Complex Concentrate for the Emergent Management of Warfarin-Associated Intracranial Hemorrhage.

BACKGROUND: Four-factor prothrombin complex concentrates (PCC) produce a more rapid and complete INR correction compared with 3-factor PCC in patients receiving warfarin. It is unknown if this improves clinical outcomes in the setting of intracranial hemorrhage (ICH). METHODS: This multicenter, retrospective cohort study included patients presenting with warfarin-associated ICH reversed with either 4- or 3-factor PCC. The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, discharge location, intensive care unit (ICU) and hospital-free days, INR reversal, and thromboembolic (TE) events at 90 days. Each was analyzed using regression analysis. Continuous and binary outcomes were analyzed using linear and logistic regression, respectively, while ordinal regression was used for discharge location. RESULTS: Of the 103 patients, 63 received 4-factor PCC. Median age was 79 years [interquartile intervals(IQI 73-84)], median presenting INR was 2.7 (2.2-3.3), and presenting ICH was intraparenchymal in 51% of patients. In-hospital and 30-day mortality were 25 and 35%, respectively. In-hospital mortality was greater among those who received 4-factor PCC, yet was not statistically significant (OR 2.2, 95% CI 0.59-9.4, p = 0.26), as having Glasgow Coma Scale (GCS) ≤8 explained most of the difference (OR 48, 95% CI 14-219, p <0.001). The effect of 4-factor PCC was not statistically significant in any of the secondary analyses. Crude rates of TE events were higher in the 4-factor PCC group (19 vs. 10%), though not significantly. CONCLUSIONS: In-hospital mortality was not improved with the use of 4- versus 3-factor PCC in the emergent reversal of warfarin-associated ICH. Secondary clinical outcomes were similarly nonsignificant.