Kerry Mohrien

Remifentanil, ketamine, and fospropofol: a review of alterative continuous infusion agents for sedation in the critically ill.

Sedation and analgesia are integral aspects in the care of critically ill patients admitted to the intensive care unit. In recent years, many of the commonly used sedative agents in the United States have experienced manufacturing and sterility issues leading to decreased availability. In addition, current practice has shifted to providing lighter levels of sedation as clinicians have gained a better understanding of the consequences of prolonged deep sedation. Benzodiazepines have fallen out of favor due to findings including increased delirium and duration of mechanical ventilation. Alterations in end-organ function in critically ill patients may also lead to varied responses to commonly used sedatives. With numerous factors impacting choice of sedation in the intensive care unit, fospropofol, ketamine, and remifentanil have been considered potential alternatives to standard therapy. The purpose of this review was to discuss strategies for the safe and effective use of fospropofol, ketamine, and remifentanil for continuous intravenous sedation in critically ill patients.

Continuous intravenous antiarrhythmic agents in the intensive care unit: strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

The development of cardiac arrhythmias in the intensive care unit is common and associated with poor prognoses and outcomes. Because of the complexity of patients admitted to the intensive care unit, the management of arrhythmias is often difficult and may require multiple therapeutic interventions. In order for clinicians to appropriately manage arrhythmias, a thorough understanding of all available therapies, including intravenous antiarrhythmic agents, is essential. Suitable antiarrhythmic agents for use in the critical care setting include amiodarone, lidocaine, and procainamide. While these agents can be effective in managing cardiac arrhythmias, they also possess significant disadvantages and require additional monitoring during use. Therapy with these agents is often complicated because of the presence of significant associated adverse effects, clinician unfamiliarity, variable dosing strategies, and the potential for drug-drug interactions. The purpose of this review is to discuss indications and strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

Effects of propofol on vasopressor use in patients with sepsis and severe sepsis: A pilot study

PURPOSE Propofol is one of the most commonly used sedatives in the intensive care unit (ICU) despite its undesirable hypotensive effects. The purpose of this study was to determine the effects of continuous intravenous (CIV) propofol on vasopressor requirements in mechanically ventilated patients with sepsis. MATERIALS AND METHODS A multicenter, retrospective, propensity-matched pilot study was conducted comparing patients with sepsis or severe sepsis who received CIV propofol for sedation to those who did not. The primary outcome was incidence of vasopressor support. Secondary outcomes included change in mean arterial pressure, mortality, and length of stay. RESULTS A total of 279 patients (149 CIV propofol, 130 non-CIV propofol) were evaluated, with 174 patients matched 1:1 based on propensity score. There was no difference in vasopressor support requirements (49.4% vs 54%; P= .65) or in those experiencing a greater than 20% decrease in mean arterial pressure from baseline (58.6% vs 63.2%; P= .53) in the CIV propofol and non-CIV propofol groups. Furthermore, there were no differences in any secondary outcomes including hospital mortality (32.2% vs 33.3%; P= .87). CONCLUSIONS Continuous intravenous propofol for sedation did not increase vasopressor requirements in this septic population. Furthermore, CIV propofol was not associated with significant differences in the use of multiple vasopressors, change in mean arterial pressure, length of stay, or mortality.

548: IMPACT OF OBESITY ON RESPONSE TO 3-FACTOR AND 4-FACTOR PROTHROMBIN COMPLEX CONCENTRATE

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Factor Xa (FXa) inhibitors are used for prevention and treatment of venous thromboembolism and prevention of stroke in patients with non-valvular atrial fibrillation (AF). Specific reversal agents are not available, thus four-factor prothrombin complex concentrate (4FPCC) is often used to reverse anticoagulant effects in the event of serious hemorrhage. The objective of this study was to evaluate the efficacy and safety of 4F-PCC for acute major hemorrhage associated with FXa inhibitors. Methods: A single center retrospective chart review of adults who received 4F-PCC for acute major hemorrhage while taking apixaban, rivaroxaban, or edoxaban from August 2013 October 2016 was performed. Patients were excluded if they were transitioned to comfort care within 24 hours of receiving 4F-PCC or if post-administration CT scans were unavailable for assessment of hemostasis in patients with intracranial hemorrhage (ICH). The primary endpoint of the study was percentage of patients who achieved hemostasis. Secondary endpoints included dose of 4F-PCC, receipt of fresh frozen plasma (FFP), incidence of thromboembolic events, and in-hospital mortality. Data were analyzed descriptively. Results: Twenty-eight patients were screened and 22 met inclusion criteria (14 apixaban, 8 rivaroxaban). The mean age was 77 ± 12 years, 69% were male, and 59% were receiving anticoagulation for AF. Sixty-eight percent of patients were receiving FXa inhibitor doses consistent with manufacturer labeling. The location of hemorrhage was ICH in 54.5%, gastrointestinal (GI) in 31.8%, and other sites in 18.2% of patients. The mean dose of 4F-PCC was 30 ± 7 units/kg. Hemostasis was achieved in 90.9% of patients. Overall, 27.3% of patients also received FFP. Two patients experienced deep vein thrombosis after 4F-PCC and in-hospital mortality was 9.1%. Conclusions: In the setting of acute major hemorrhage associated with FXa inhibitors, 4F-PCC was safe and effective in achieving hemostasis. To our knowledge, this is the first study to evaluate 4F-PCC to reverse FXa inhibitors for major hemorrhage not limited to ICH.

745: SAFETY AND EFFICACY OF ATYPICAL ANTIPSYCHOTICS FOR ALCOHOL WITHDRAWAL IN SURGICAL INTENSIVE CARE

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Benzodiazepines are considered first line in the management of alcohol withdrawal syndrome (AWS). However, patients who develop psychosis or delirium may require an adjunct antipsychotic. Atypical antipsychotics may have an enhanced safety profile compared to typical antipsychotics, but minimal literature supports their use. This study evaluates the effect of atypical antipsychotics on benzodiazepine requirements and sedation levels in the treatment of AWS. Methods: Single center, retrospective cohort study of patients admitted to the surgical intensive care unit at Temple University Hospital between January 1, 2012 – June 30, 2016 who received benzodiazepines with or without an atypical antipsychotic for AWS. The two groups were compared for differences in the percentage of time spent at goal RASS (Richmond Agitation Sedation Scale) score, benzodiazepine requirements, duration of benzodiazepine use, QTc prolongation, and seizures. Results: Thirty-nine patients were included, 28 (72%) receiving benzodiazepines alone and 11 (28%) receiving an atypical antipsychotic in addition to benzodiazepines. At baseline, a greater percentage of patients in the combination group had a history of severe AWS and chronic benzodiazepine use. The combination group spent less time at goal RASS compared to the benzodiazepine alone group (39% vs. 57%, p = 0.008). The median benzodiazepine dose per day in lorazepam equivalents, (17.7 mg vs. 6.2 mg, p = 0.054) and duration of benzodiazepine use (14.0 days vs. 5.5 days, p = 0.003) was greater in the combination group. The median daily benzodiazepine dose in the combination group decreased after the addition of the atypical antipsychotic (38.6 mg vs. 12.5 mg, p = 0.53) when compared four days prior to and after its addition. There were no differences in the incidence of QTc prolongation or seizures. Conclusions: Atypical antipsychotics appear to be safe when used as adjunct therapy in the management of AWS. The addition of an atypical antipsychotic may result in decreased benzodiazepine requirements in patients with severe AWS although confirmation in a larger population is needed.

657: PENETRATION OF DAPTOMYCIN INTO PLEURAL SPACE DURING TREATMENT OF MULTIDRUG-RESISTANT VRE EMPYEMA

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Antibiotic selection for the treatment of multidrug resistant empyema can be complicated due to a lack of information regarding antimicrobial penetration to the pleural space. We present a rare case of vancomycin resistant Enterococcus faecium (VRE) cultured in pleural fluid and treated with high dose daptomycin. Due to limited sensitivities and a lack of information supporting the penetration of daptomycin into the pleural space, serum and pleural fluid concentrations were obtained to guide treatment. Methods: A 60 year old female with an extensive medical history notable for nonspecific interstitial pneumonia presented with severe hypoxic respiratory failure and eventually underwent a right lung transplantation. After transplantation, the patient remained critically ill with a complicated course including the development of a right sided empyema requiring chest tube placement. Results: The patient was treated empirically with vancomycin and meropenem, dose adjusted for moderate renal impairment, while pleural fluid was sent for culture and analysis. Microbiology results showed VRE with intermediate sensitivity to linezolid and a daptomycin MIC of 4 mcg/ml. Four days following chest tube placement, therapy was changed to daptomycin (8 mg/kg). Steady state serum and pleural concentrations were obtained at 0.5, 4.5 and 24 hours post administration. Serum: pleural results were 133.8: 21.4, 119.6: 24.4, and 67.6: 32.5 μg/ml respectively. After three days of daptomycin monotherapy, the dose was increased to 10 mg/kg due to the high MIC and synergistic ampicillin was utilized for 15 days to enhance cell membrane binding. Repeat pleural fluid cultures cleared after 11 days of synergistic of treatment, chest tube drainage, and one surgical debridement. Total daptomycin treatment duration was four weeks in which no adverse effects were noted. The patient remains critically ill with a prolonged hospital admission unrelated to this case. This case is the first to our knowledge to describe the penetration of daptomycin into pleural space for the treatment of an empyema caused by VRE.

463: FIXED WEIGHT-BASED DOSING OF 3-FACTOR PCC FOR WARFARIN REVERSAL IN ICH IS SAFE AND EFFICACIOUS

Introduction: Anticoagulation with warfarin is associated with numerous adverse events and complications, the most significant being intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is recommended for international normalization ratio (INR) reversal, however data regarding its us