Pharmacokinetics of Levetiracetam Seizure Prophylaxis in Severe Traumatic Brain Injury.

Background: Drug pharmacokinetics (PK) are altered in neurocritically ill patients, and optimal levetiracetam dosing for seizure prophylaxis is unknown.

Objective: This study evaluates levetiracetam PK in critically ill patients with severe traumatic brain injury (sTBI) receiving intravenous levetiracetam 1000 mg every 8 (LEV8) to 12 (LEV12) hours for seizure prophylaxis.

Methods: This prospective, open-label study was conducted at a level 1 trauma, academic, quaternary care center.

Antibiotic Duration Following Abdominal Gunshot Injuries With Associated Pelvis or Spine Involvement: A 20-Year Single-Center Experience.

Introduction: Optimal antimicrobial prophylaxis duration following gunshot wounds (GSW) to the abdomen with an associated orthopedic fracture is unknown. This study evaluated the safety and efficacy of short versus long courses of prophylactic antibiotics following penetrating hollow viscus injury with communicating orthopedic fracture.

Methods: This retrospective study included adult patients admitted to the trauma service over a 20-y period who sustained an abdominal GSW with hollow viscus injury and communicating spine or pelvic fractures.

Comparison of Doxycycline or Minocycline to Sulfamethoxazole-Trimethoprim for Treatment of Pneumonia.

Background: is a multidrug-resistant organism with limited antibiotic treatment options. Minocycline and doxycycline may be appropriate, but clinical data are limited.

Objective: To compare tetracyclines (minocycline and doxycycline [TCN]) with standard of care, sulfamethoxazole-trimethoprim (TMP-SMZ), in pneumonia treatment.

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures.

Background: Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24 h of an invasive procedure.

Methods: This single-center, observational, retrospective study included patients who received andexanet alfa within 24 h of an invasive or surgical procedure.

Case Report: Extended Duration Andexanet Alfa Infusion in a Surgical Trauma Patient.

Andexanet alfa (andexanet) is the only FDA-approved medication for reversal of apixaban and rivaroxaban anticoagulation for life-threatening or uncontrolled bleeding. Infusion modifications may be required in surgical patients undergoing prolonged operative intervention but have not previously been described. A 78-year-old woman on rivaroxaban for atrial fibrillation was admitted to the trauma service for a mechanical fall, sustaining a T4 burst fracture with severe canal stenosis and spinal cord edema resulting in loss of strength and sensation in her legs.

Retrospective Evaluation of Intrapleural Tissue Plasminogen Activator With or Without Dornase Alfa for the Treatment of Traumatic Retained Hemothorax: A 6-Year Experience.

Background: Intrapleural fibrinolytic instillation is second-line treatment for retained hemothorax. Dornase alfa (DNase) has demonstrated efficacy in parapneumonic effusion, but the lack of deoxyribonucleoproteins limits direct extrapolation to traumatic retained hemothorax treatment.

Objective: This study evaluated the effectiveness of intrapleural tissue plasminogen activator (tPA) with and without DNase in the treatment of retained traumatic hemothorax.

Assessment of Detectable Serum Tobramycin Concentrations in Patients Receiving Inhaled Tobramycin for Ventilator-Associated Pneumonia.

Background: Inhaled tobramycin can be used for empiric or definitive therapy of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. This is believed to minimize systemic exposure and potential adverse drug toxicities including acute kidney injury (AKI). However, detectable serum tobramycin concentrations have been reported after inhaled tobramycin therapy with AKI.

Applying Cefepime Population Pharmacokinetics to Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

Patients admitted to the intensive care unit (ICU) may need continuous renal replacement therapy (CRRT) due to acute kidney injury or worsening of underlying chronic kidney disease. This will affect their antimicrobial exposure and may have a significant impact on the treatment. We aim to develop a cefepime pharmacokinetic (PK) model in CRRT ICU patients and generate the posterior predictions for a group and assess their therapy outcomes.

Clinical Experience, Characteristics, and Performance of an Acetaminophen Absorption Test in Critically Ill Patients.

Background: Altered drug and nutrient absorption presents a unique challenge in critically ill patients. Performing an acetaminophen absorption test (AAT) has been used as a marker for gastric motility and upper small bowel absorption; thus, it may provide objective data regarding enteral absorptive ability in critically ill patients.

Study Question: What is the clinical experience with AAT when used as a surrogate marker for enteral absorption in critically ill patients?

Study Design: This single-center, retrospective, cohort study evaluated serum acetaminophen concentrations within 180 minutes following 1-time enteral administration of an AAT.

Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial.

The impact of antithrombin III activity (AT-III) on prophylactic enoxaparin anti-factor Xa concentration (anti-Xa) is unknown in high-risk trauma patients. So too is the optimal anti-Xa-adjusted enoxaparin dosage. This prospective, randomized, pilot study sought to explore the association between AT-III and anti-Xa goal attainment and to preliminarily evaluate two enoxaparin dosage adjustment strategies in patients with subprophylactic anti-Xa.

Impact of Weight on Anti-Xa Attainment in High-Risk Trauma Patients on Enoxaparin Chemoprophylaxis.

Background: Serum anti-factor Xa (anti-Xa) concentration may guide low molecular weight heparin chemoprophylaxis in trauma patients. Higher total body weight (TBW) is a risk factor for subprophylactic anti-Xa and venous thromboembolism (VTE). The purpose of this study was to evaluate TBW differences in patients with subprophylactic versus prophylactic trough anti-Xa.

Cefepime Population Pharmacokinetics and Target Attainment in Critically Ill Patients on Continuous Renal Replacement Therapy.

Sepsis causes half of acute kidney injuries in the intensive care unit (ICU). ICU patients may need continuous renal replacement therapy (CRRT), which will affect their antimicrobial exposure. We aimed to build a cefepime population pharmacokinetic (PK) model in CRRT ICU patients and perform simulations to assess target attainment.

Retrospective Evaluation of Venous Thromboembolism Prophylaxis in Elderly, High-Risk Trauma Patients.

Background: Venous thromboembolism (VTE) risk increases with age. Scarce data exist for patients age ≥65 y. This study evaluated VTE incidence in elderly, high-risk trauma patients receiving unfractionated heparin (UFH) or enoxaparin chemoprophylaxis.

COPD Care Bundle in Emergency Department Observation Unit Reduces Emergency Department Revisits.

Background: COPD exacerbations lead to accelerated decline in lung function, poor quality of life, and increased mortality and cost. Emergency department (ED) observation units provide short-term care to reduce hospitalizations and cost. Strategies to improve outcomes in ED observation units following COPD exacerbations are needed.

Multidisciplinary Team Utilizing Pharmacists in Multimodal, Bundled Care Reduce Chronic Obstructive Pulmonary Disease Hospital Readmission Rates.

Background: Chronic obstructive pulmonary disease (COPD) is a major contributor of morbidity and mortality in the United States resulting in high hospitalization and readmission rates. For health systems, identifying an effective strategy to reduce COPD readmissions has remained difficult. Multiple COPD care bundles have been developed with varying degrees of success.

Pharmacokinetics and Pharmacodynamics of Extended-Infusion Cefepime in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Prospective, Open-Label Study.

Study Objective: To evaluate extended-infusion (EI) cefepime pharmacokinetics (PK) and pharmacodynamic target attainment in critically ill patients receiving continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD).

Design: Prospective, open-label, PK study.

Setting: Intensive care units at a large, academic, tertiary-care medical center.

Continuous Infusion Ketamine for Adjunctive Analgosedation in Mechanically Ventilated, Critically Ill Patients.

Objective: Ketamine is an N-methyl-D-aspartate antagonist with emerging evidence assessing its use as a continuous infusion agent to provide concomitant analgesia and sedation. The role of ketamine as adjunctive therapy in mechanically ventilated patients is unclear. This study sought to investigate the impact of adjunctive continuous infusion ketamine on concomitant analgesic and sedative dosing while providing goal comfort in mechanically ventilated patients.

Evaluation of Thrombocytopenia in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

Background: Continuous renal replacement therapy (CRRT) may be associated with thrombocytopenia in critically ill patients. A confounding factor is concomitant use of unfractionated heparin (UFH) and suspicion for heparin-induced thrombocytopenia (HIT).

Objective: To determine the impact of CRRT on platelet count and development of thrombocytopenia.

Ketamine versus hydromorphone patient-controlled analgesia for acute pain in trauma patients.

Background: It is unknown whether ketamine administered via patient-controlled analgesia (PCA) provides adequate analgesia while reducing opioid consumption in the traumatically injured patient. Differences in opioid consumption, pain scores, and adverse effects between ketamine and hydromorphone PCA were studied.

Materials And Methods: This is an investigator-initiated, single-center, double-blinded, randomized, pilot trial conducted from 2014 to 2016 at a level 1 trauma center.

Integrated Process Modeling-A Process Validation Life Cycle Companion.

During the regulatory requested process validation of pharmaceutical manufacturing processes, companies aim to identify, control, and continuously monitor process variation and its impact on critical quality attributes (CQAs) of the final product. It is difficult to directly connect the impact of single process parameters (PPs) to final product CQAs, especially in biopharmaceutical process development and production, where multiple unit operations are stacked together and interact with each other. Therefore, we want to present the application of Monte Carlo (MC) simulation using an integrated process model (IPM) that enables estimation of process capability even in early stages of process validation.

Workflow for Criticality Assessment Applied in Biopharmaceutical Process Validation Stage 1.

Identification of critical process parameters that impact product quality is a central task during regulatory requested process validation. Commonly, this is done via design of experiments and identification of parameters significantly impacting product quality (rejection of the null hypothesis that the effect equals 0). However, parameters which show a large uncertainty and might result in an undesirable product quality limit critical to the product, may be missed.

Early Prediction Tool to Identify the Need for Pharmacotherapy in Infants at Risk of Neonatal Abstinence Syndrome.

Objective: To develop a tool to predict the need for pharmacologic treatment of neonatal abstinence syndrome (NAS) within 36 hours from birth in infants at risk for opioid withdrawal.

Study Design: Retrospective study of infants born at gestation of ≥34 weeks with in utero exposure to opioids during two time periods from January 2013 through October 2016. Period 1 was used to develop a predictive tool for validation during period 2.

Development of the Critical Care Pharmacotherapy Trials Network.

Purpose: The development of the Critical Care Pharmacotherapy Trials Network (CCPTN) as a model for practice-based pharmacotherapy research is described.

Summary: The CCPTN was formed in 2010 as a collaborative research network dedicated to scientific investigation in the field of critical care pharmacotherapy. The CCPTN organizational structure is consistent with many professional pharmacy and interdisciplinary organizations and organized into 3 primary domains: executive committee, working committees, and network membership.

Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis.

Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes.