Difficulties Detecting Clinically Relevant Factor Xa Inhibitor Levels Prior to Reversal With Andexanet Alfa for Intracranial Hemorrhage.

Coagulation factor Xa (recombinant), inactivated-zhzo (andexanet alfa) is approved for reversal of life-threatening bleeding with rivaroxaban and apixaban use. Clinical decision-making to initiate reversal is reliant on dose taken and timing of last dose. In practice, timing of last dose may be unknown, and the turnaround time for drug-specific anti-factor Xa levels at some institutions may be prolonged, leaving clinicians balancing a difficult decision with limited tools. This report includes a series of 3 patients who presented to our institution with an intracranial hemorrhage and received andexanet alfa for apixaban reversal. These cases highlight the challenges clinicians are facing when using andexanet alfa for emergent rivaroxaban or apixaban reversal when the timing of last dose is unknown, or patients fall outside of the recommended timeframe for use and clinically relevant drug levels are still suspected. Based on our experiences, we encourage other institutions to evaluate their abilities to rapidly and accurately detect the presence of clinically relevant rivaroxaban and apixaban levels when utilizing andexanet alfa.

Pentobarbital Coma Use in a Pregnant Patient With Refractory Intracranial Hypertension: A Case Report.

OBJECTIVE: Intracranial hypertension is a life-threatening condition that requires emergent diagnosis and management. Although pentobarbital coma for refractory intracranial hypertension has been studied in the general population, this study is the first reported case of pentobarbital coma use in a pregnant patient. METHODS: We performed a retrospective chart review of a pregnant patient with refractory intracranial hypertension and reviewed the current literature on the role of pentobarbital coma. RESULTS: We present the case of a 35-year-old woman at 26 weeks of gestation who developed refractory intracranial hypertension secondary to rupture of a dural arteriovenous fistula. The patient was taken to surgery for decompressive hemicraniectomy, clot evacuation, and dural arteriovenous fistula resection. Subsequently, the patient was treated with pentobarbital coma for 5 days and achieved adequate control of her intracranial pressures. The patient and fetus were closely monitored by the obstetrics team with no apparent harm to fetal well-being during her hospital stay. The patient underwent planned cesarean delivery at term, and both the mother and newborn were discharged in stable condition with no known pentobarbital-related complications. CONCLUSIONS: Thus, we present the first case report demonstrating that pentobarbital coma may be a safe and efficacious option for treating pregnant patients with life-threatening refractory intracranial hypertension. We also provide dosing information for pentobarbital administration. Additional studies and reports involving pregnant patients are needed to better understand the impact of pentobarbital on both the mother and fetus. Furthermore, long-term follow-up of both the mother and newborn is critical to identifying any delayed sequelae of neonatal exposure to pentobarbital.

Enhanced renal clearance and impact on vancomycin pharmacokinetic parameters in patients with hemorrhagic stroke.

BACKGROUND: The majority of patients with hemorrhagic stroke experience enhanced renal clearance or augmented renal clearance (ARC). The purpose of this study was to determine the impact of enhanced renal clearance or ARC on vancomycin pharmacokinetic (PK) parameters. METHODS: This was a post hoc analysis of a prospective study of adult patients with aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH) admitted to the neurosciences intensive care unit who received vancomycin. Creatinine clearance (CrCl) was measured and also estimated using the Cockcroft-Gault equation. Predicted PK parameters were compared with calculated PK parameters using serum peak and trough concentrations. RESULTS: Seventeen hemorrhagic stroke patients met inclusion criteria. All patients experienced enhanced renal clearance on the day that the vancomycin concentrations were obtained, and 12 patients (71%) experienced ARC. The mean calculated elimination rate constant was significantly higher than the predicted value (0.141 ± 0.02 vs. 0.087 ± 0.01 h-1; p = 0.004) and the mean calculated half-life was significantly lower than the predicted half-life (6.5 ± 0.9 vs. 8.7 ± 0.6 h; p = 0.03). CONCLUSIONS: Patients with hemorrhagic stroke and enhanced renal clearance displayed PK alterations favoring an increased elimination of vancomycin than expected. This may result in underexposure to vancomycin, leading to treatment failure.

Enhanced Renal Clearance in Patients With Hemorrhagic Stroke.

OBJECTIVES: To evaluate enhanced renal clearance over time in patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage via measured creatinine clearance and to compare measured creatinine clearance to creatinine clearance calculated by the Cockcroft-Gault equation and estimated glomerular filtration rate calculated by the Modification of Diet in Renal Diseases equation. DESIGN: Prospective, observational study. SETTING: Neurosciences ICU in a tertiary care academic medical center. PATIENTS: Study participants had an admission diagnosis of aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage, an expected neurosciences ICU length of stay greater than 48 hours, no evidence of renal dysfunction (admission serum creatinine < 1.5 mg/dL), and no history of chronic kidney disease. INTERVENTIONS: Eight-hour urine collections to measure creatinine clearance were collected daily as the primary method of measuring renal function. Creatinine clearance was also calculated using the Cockcroft-Gault equation and estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Enhanced renal clearance was defined as a measured creatinine clearance greater than the calculated creatinine clearance via Cockcroft-Gault and estimated glomerular filtration rate via Modification of Diet in Renal Disease. Augmented renal clearance was defined by a measured creatinine clearance greater than or equal to 130 mL/min/1.73 m. Relevant demographic, clinical, and outcome data were recorded. MEASUREMENTS AND MAIN RESULTS: Fifty aneurysmal subarachnoid hemorrhage patients and 30 intracerebral hemorrhage patients were enrolled, contributing 590 individual measurements. Patients with aneurysmal subarachnoid hemorrhage had a higher mean measured creatinine clearance compared with the mean calculated creatinine clearance based on the Cockcroft-Gault equation (147.9 ± 50.2 vs 109.1 ± 32.7 mL/min/1.73 m; p < 0.0001) and higher mean measured creatinine clearance compared with the mean calculated estimated glomerular filtration rate based on the Modification of Diet in Renal Disease equation (147.9 ± 50.2 vs 126.0 ± 41.9 mL/min/1.73 m; p = 0.04). Ninety-four percent of participants with aneurysmal subarachnoid hemorrhage experienced augmented renal clearance on at least 1 day. In patients with intracerebral hemorrhage, there was a higher mean measured creatinine clearance over the study period compared with the mean calculated creatinine clearance (119.5 ± 57.2 vs 77.8 ± 27.6 mL/min/1.73 m; p < 0.0001) and higher mean measured creatinine clearance compared with the mean calculated estimated glomerular filtration rate based on the Modification of Diet in Renal Disease equation (119.5 ± 57.2 vs 93.0.0 ± 32.8 mL/min/1.73 m; p = 0.02). Fifty percent of participants with intracerebral hemorrhage experienced augmented renal clearance on at least 1 day. CONCLUSIONS: A substantial group of patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage experienced enhanced renal clearance, which may be otherwise unknown to clinicians. Enhanced renal clearance may lead to increased renal solute elimination over what is expected, resulting in subtherapeutic renally eliminated drug concentrations. This may result in underexposure to critical medications, leading to treatment failure and other medical complications.

Energy Expenditure in Critically Ill Adult Patients With Acute Brain Injury: Indirect Calorimetry vs. Predictive Equations.

Introduction: Predictive equations (PE) are used in lieu of indirect calorimetry (IC) due to cost and limited resources; however, these equations may not be as accurate as IC in estimating resting energy expenditure (REE) in critically ill patients, putting them at risk of malnutrition. The purpose of this study is to compare predicted and measured energy expenditure (MEE) in critically ill adults with acute brain injury. Materials and Methods: This was a retrospective review of adult patients admitted to the Neurosciences ICU with acute brain injury between May 1st, 2014 and April 1st, 2016 who had IC performed. The Harris Benedict (HBE), Penn State University, and Mifflin St Jeor (MSJ) PE were used in comparison to IC results. Subgroup analyses stratified patients based on BMI and type of acute brain injury. Results: One hundred and forty-four patients met inclusion criteria. Comparing predicted and MEE found no significant difference (p = 0.1). High degrees of interpatient variability were discovered, with standard deviations ranging from 17 to 29% of each PE. Pearson's correlations indicated weak associations when HBE, Penn State, and MSJ were individually compared to MEE (r = 0.372, 0.409, and 0.372, respectively). A significant difference was found between predicted and MEE in patients with a BMI < 30 kg/m2 (p < 0.01) and in those with aneurysmal subarachnoid hemorrhage (p < 0.01). Discussion: Due to interpatient variability that exists among REE of critically ill patients with acute brain injury, IC should be used when feasible.

Correction to: Influence of Single-Dose Antibiotic Prophylaxis for Early-Onset Pneumonia in High-Risk Intubated Patients.

Due to an error introduced during the production process, J. Dedrick Jordan's name was improperly tagged in the original publication of this article. It is tagged correctly here.

Influence of Single-Dose Antibiotic Prophylaxis for Early-Onset Pneumonia in High-Risk Intubated Patients.

BACKGROUND: Early-onset pneumonia (EOP) after endotracheal intubation is common among critically ill patients with a neurologic injury and is associated with worse clinical outcomes. METHODS: This retrospective cohort study observed outcomes pre- and post-implementation of an EOP prophylaxis protocol which involved the administration of a single dose of ceftriaxone 2 g around the time of intubation. The study included patients ≥ 18 years who were admitted to the University of North Carolina Medical Center (UNCMC) neuroscience intensive care unit (NSICU) between April 1, 2014, and October 26, 2016, and intubated for ≥ 72 h. RESULTS: Among the 172 patients included, use of an EOP prophylaxis protocol resulted in a significant reduction in the rate of microbiologically confirmed EOP compared to those without prophylaxis (7.4 vs 19.8%, p = 0.026). However, EOP prophylaxis did not decrease the combined incidence of microbiologically confirmed or clinically suspected EOP (32.2 vs 37.4%, p = 0.523). No difference in the rate of late-onset pneumonia (34.6 vs 26.4%, p = 0.25) or virulent organism growth (19.8 vs 14.3%, p = 0.416) was observed. No difference was observed in the duration of intubation, duration of intensive care unit (ICU) stay, duration of hospitalization, or ICU antibiotic days within 30 days of intubation. In hospital mortality was found to be higher in those who received EOP prophylaxis compared to those who did not receive prophylaxis (45.7 vs 29.7%, p = 0.04). CONCLUSIONS: The administration of a single antibiotic dose following intubation may reduce the incidence of microbiologically confirmed EOP in patients with neurologic injury who are intubated ≥ 72 h. A prophylaxis strategy does not appear to increase the rate of virulent organism growth or the rate of late-onset pneumonia. However, this practice is not associated with a decrease in days of antibiotic use in the ICU or any clinical outcomes benefit.