Water-soluble vitamin-E for enhancing fluorescence diagnosis in infected human dentine treated with NaOCl.

INTRODUCTION: Bacterial fluorescence methods are of interest in endodontics for informing endpoints for debridement. This study explored potential fluorescence quenching reversal effects of a water-soluble vitamin E conjugate (d-α-Tocopherol polyethylene glycol 1000 succinate, TPGS) when applied to polymicrobial biofilms grown on dentine that had been exposed to sodium hypochlorite (NaOCl) to cause quenching. METHOD: Extracted human teeth were debrided, embedded in transparent acrylic resin and sectioned. After smear layer removal, tooth dentine sections were inoculated with a polymicrobial inoculum, and cultured for 7 days to create biofilms. Samples (n = 8 per group) were exposed to 1 % or 4 % NaOCl for 2 or 4 min, and then treated with TPGS. Bacterial fluorescence readings under laser excitation at 655 nm were assessed over 10 min using a calibrated DIAGNOdent device. All data were assessed for normality (Kolmogorov-Smirnov test) and analysed with ANOVA followed by Bonferroni post-hoc tests. RESULTS: NaOCl at both concentrations quenched fluorescence readings of biofilms grown on dentine samples, with a maximal reduction of 40.4 % at 5 min after 4 % NaOCl. Treatment with TPGS gave faster recovery of fluorescence readings compared to the control at 5 and 10 min. CONCLUSION: The water-soluble antioxidant TPGS partially reversed fluorescence quenching caused by NaOCl. This agent may have value clinically for reducing the time needed for fluorescence readings to recover when NaOCl is used as an irrigant. This will facilitate more accurate assessment of endpoints for canal debridement.

Vancomycin removal and pharmacokinetics during accelerated venovenous hemofiltration.

INTRODUCTION: Vancomycin pharmacokinetics are affected by renal replacement therapy and physiologic changes in critically ill patients. Literature regarding vancomycin removal and pharmacokinetics during accelerated venovenous hemofiltration (AVVH), a form of prolonged intermittent renal replacement therapy, is limited. OBJECTIVE: To describe the removal and pharmacokinetics of vancomycin during AVVH. METHODS: Eighteen critically ill adults receiving vancomycin and AVVH were included. Vancomycin serum concentrations were obtained within 4 h before and 2-6 h after the AVVH session. Patients' serum concentrations were plotted against time, and individual pharmacokinetic parameters were determined by a one-compartmental analysis. Continuous data are reported as a median (interquartile range [IQR]) and categorical data as a percentage. RESULTS: The median AVVH effluent rate was 39.3 mL/kg/h (IQR 35.5-48 mL/kg/h) for a duration of 9 h (IQR 8-9.75 h). AVVH decreased vancomycin concentrations by 29.8% (IQR 24.9%-35.9%), at a rate of 3.4% per hour (IQR 3.1%-4.3% per hour) of AVVH. The vancomycin elimination rate constant and half-life were 0.039 h-1 (IQR 0.036-0.053 h-1 ) and 17.6 h (IQR 13.1-18.8 h), respectively. The area under the curve during AVVH was 171.7 mg*h/L (IQR 149.1-190 mg*h/L). The volume of distribution in 10 patients was 1 L/kg (IQR 0.73-1.1 L/kg). After AVVH, vancomycin 1000 mg (IQR 750-1000 mg) was needed to maintain a serum trough concentration ≥15 mg/L. CONCLUSION: Vancomycin is significantly removed by AVVH, which requires supplemental dosing after completion of the AVVH session to maintain desired serum concentrations. Therapeutic drug monitoring of vancomycin serum concentrations is recommended for patients undergoing AVVH.

Efficacy and Safety of Immediate-Release Nifedipine in Critically Ill Patients.

Background: Immediate-release nifedipine (IRN) is a calcium channel blocker with potent vasodilatory and antihypertensive properties. Safety concerns led to a black box warning for increased risk of myocardial infarction, stroke, and arrhythmias. Objective: The aim of this study was to evaluate the safety and efficacy of IRN for acute blood pressure lowering in critically ill patients. Methods: A retrospective, single-center study was performed in critically ill patients who received at least one dose of IRN. The primary endpoint was the change in systolic blood pressure (SBP) measured at baseline and 1 hour after first administration of IRN. Secondary outcomes included clinically significant hypotension, defined as an absolute reduction in SBP ≥ 15% or vasopressor initiation within 1 hour after administration; incidence of arrhythmias, stroke, or myocardial injury; and time to transition off antihypertensive infusions. Results: IRN resulted in a median [interquartile range] SBP change of -10 [-21 to -1] mmHg between baseline 142 mmHg [124-155] and 1 h post-administration 127 mmHg [114-144]; P < .001. Twenty-seven percent of patients experienced clinically significant hypotension, with hypotension observed in 24% and vasopressors initiated in 4% of patients. Sixteen percent of patients experienced new-onset arrhythmia and 18% experienced myocardial injury following IRN during hospitalization. Median time to transition off intravenous (IV) continuous infusion antihypertensives was 8.5 [0-31.5] hours. Conclusion: IRN led to a reduction in SBP which may have been associated with clinically significant hypotension and need for vasopressor support. Further studies with direct comparisons to alternatives are needed to determine the true association of adverse events with IRN.

Economic Evaluation of a Pharmacist-Led 5-Day Therapeutic Hold of IV Levothyroxine at an Academic Medical Center.

Objective: Providers often admit patients with active outpatient prescriptions for levothyroxine. During an inpatient admission, providers may instruct critically ill patients to take nothing by mouth, or nil per os (NPO). Thus, they may prescribe the intravenous (IV) formulation of levothyroxine during this period. However, levothyroxine possesses a prolonged half-life of up to 7 days; therefore, immediate transition to IV levothyroxine may not be clinically necessary in the acute NPO setting. Intravenous levothyroxine is significantly more expensive than equivalent oral doses and may prove to be a financial burden for an institution. By understanding the pharmacokinetic properties of levothyroxine, we implemented a cost-saving initiative involving a 5-day therapeutic hold of IV levothyroxine. Methods: This was a retrospective evaluation in 2 intensive care units (ICU): a 20-bed surgical/trauma ICU and an 18-bed mixed medical/surgical ICU. Patient data, utilization data, and documented pharmacist interventions were collected for 6 months prior to implementation of the 5-day IV levothyroxine therapeutic hold and for 6 months post-implementation. All patients prescribed IV levothyroxine during these timeframes were included. Results: During the 6-month pre-implementation phase, 674 doses (691 vials) of IV levothyroxine for 77 unique patients were dispensed from the 2 ICUs. During the 6-month post-implementation phase, 168 doses (188 vials) of IV levothyroxine were dispensed for 44 unique patients. Of the 44 patients (48 orders) who still received IV levothyroxine, 22.9% of orders were deemed clinically necessary by the pharmacist and were not recommended to be held under the protocol, 64.6% were due to the verifying pharmacist being unaware of the protocol, 8.3% of orders were due to protocol non-compliance, and 4.2% were verified after the 5-day hold was complete as the patient remained NPO. This pharmacy-led initiative resulted in a 75% decrease in usage post-implementation and an estimated annualized savings of $80,000. Conclusion: A pharmacy-led initiative comprised of a 5-day therapeutic hold of IV levothyroxine was feasible and led to a 75% reduction in usage and cost over a 6-month period in 2 ICU's. Future steps include additional staff education for improved protocol adherence and expanding the protocol institution-wide for an even greater cost-savings potential.

A Pharmacy Quality and Internal Audit Program Promoting Continuous Survey Readiness with Medication Management Standards.

BACKGROUND: Showcasing compliance with Joint Commission Medication Management (MM) standards during accreditation visits is important, but it is equally vital to maintain a state of continuous survey readiness. This article describes a Pharmacy Quality and Internal Audit Program to promote continuous survey readiness and sustained compliance with MM standards. METHODS: A comprehensive MM audit was developed to assess for compliance in all inpatient, ambulatory, and procedural areas that use medications, with each area undergoing the internal auditing process at least twice per calendar year. The audit is performed by an MM subject matter expert from the Department of Pharmacy and incorporates electronic chart review, clinical staff interviews, and observations of area-specific medication practices. Notable findings and recommendations are communicated to area-specific leadership. Institutionwide scorecards are compiled to track performance with MM standards, identify opportunities, and determine future focus areas to improve and sustain compliance. RESULTS: Results revealed consistent compliance (≥ 90%) with a majority of MM standards. These included hazardous medication management, controlled substances compliance, look-alike/sound-alike drugs, medication storage/security, and labeling of medication syringes. Several areas of opportunity were identified: awareness of high-alert medications and risk-reduction safety strategies, compliance with pill cutter standards, and therapeutic duplication of "as needed" medication orders. Subsequent implementation of corrective actions and mitigation strategies resulted in improved compliance rates from < 50% to ≥ 90% for awareness of high-alert medications and risk-reduction strategies, from < 60% to ≥ 80% for compliance with pill cutter standards, and from < 90% to ≥ 90% for therapeutic duplication of "as needed" orders. CONCLUSION: Establishment of a Pharmacy Quality and Internal Audit Program allowed for performance tracking, identification of compliance deficiencies, implementation of focused corrective actions, and promotion of continuous survey readiness with MM standards.

Utilising an automated medication inventory management system for emergency crash carts during the COVID-19 pandemic.

The high acuity of patients with COVID-19 during the pandemic in the city of New York correlated with an increased incidence of cardiac arrests and other emergent resuscitation scenarios requiring life-sustaining treatment. A spike in the utilisation of emergency crash cart medications was to be expected. The department of pharmacy at SUNY Downstate Health Sciences University optimised the use of an automated medication inventory management system with radio-frequency identification to assess usage and turnover of emergency crash carts; improve efficiency and turnaround times for crash cart dispatches; track drug consumption; and manage ongoing medication shortages during the peak of the COVID-19 pandemic. By capitalising on the utility and functionality of technology and automation, the institution was able to keep pace with acute patient care demands to prevent gaps in pharmaceutical care and medication management during emergency responses.

Fluorescence characteristics of E. faecalis in dentine following treatment with oxidizing endodontic irrigants.

INTRODUCTION: This study aimed to assess changes in the fluorescence characteristics of Enterococcus faecalis in human dentine over a period of 24 h following treatment with endodontic irrigants. METHOD: Sterilised, non-functional extracted third molars were embedded in acrylic resin and uniformly sectioned into 2 mm thick dentine sections. After the removal of smear layer, the dentine sections were inoculated with E. faecalis and cultured for 7 days. The infected dentine sections were subsequently treated with different concentrations of sodium hypochlorite (NaOCl) and hydrogen peroxide (H2O2). Bacterial fluorescence readings were assessed at different time points using a calibrated laser device. All data were assessed for normality (Kolmogorov Smirnoff test) and analysed using ANOVA with Bonferroni post-hoc tests. RESULTS: Fluorescence readings were quenched when E. faecalis infected human dentine sections were treated with oxidizing irrigants in vitro. Throughout a 24-hour period, fluorescence recovered in part but did not return to baseline level. CONCLUSION: The fluorescence quenching effect of these oxidizing agents needs to be considered when using laser fluorescence in assessing the quality of root canal debridement or disinfection.

COVID-19 pneumonia in kidney transplant recipients: Focus on immunosuppression management.

BACKGROUND: The coronavirus disease of 2019, also known as COVID-19, has been declared a global pandemic. Significant controversies exist regarding treatment modalities for this novel disease, especially in immunocompromised patients. Experience with management of COVID-19 in kidney transplant recipients is scarce; effects of this virus on immunosuppressed individuals are not well understood. METHODS: We identified 30 renal transplant recipients with confirmed COVID-19 pneumonia who were admitted to inpatient between March 2020 and April 2020. All patients received a 5-day course of hydroxychloroquine and azithromycin; half of the patients received methylprednisolone. During hospitalization, calcineurin inhibitors and antimetabolites were held; prednisone was continued. RESULTS: Clinical presentation of flu-like symptoms was similar to those in the general population. Hyponatremia, lymphopenia, acute kidney injury, and elevated inflammatory markers were common. Over the course of follow-up, 23 have been discharged home with a functioning allograft and in stable condition; 4 experienced acute kidney injury requiring renal replacement therapy; 7 patients were intubated, and 6 expired. The mortality rate in our cohort was 20%. CONCLUSION: Our findings described the characteristics and outcomes of this highly fatal illness in a multi-ethnic kidney transplant cohort, with insights on immunosuppression management that could further our understanding of this unique disease in immunocompromised populations.

Safety and Effectiveness of Intravenous Chlorpromazine for Agitation in Critically Ill Patients.

BACKGROUND: Agitation is common in the intensive care unit (ICU). Although antipsychotics are frequently used as first-line therapy, chlorpromazine has fallen out of favor due to risk of cardiovascular complications and severe hypotension. Although chlorpromazine is used anecdotally, there is a lack of data regarding its safety and effectiveness. The objective of this study was to investigate the use of intravenous (IV) chlorpromazine for agitation in the ICU setting. METHODS: A retrospective review was performed at a tertiary care academic medical center. Patients were included if they received IV chlorpromazine in the ICU for agitation, infused at a rate of 1 mg/min. Primary end points were change in systolic blood pressure (SBP), heart rate (HR), and mean arterial pressure (MAP) within 4 hours of administration. Secondary end points included change in vasopressor and adjunct sedative medication requirements, achievement of Richmond-Agitation Sedation Scale (RASS) 0 to -1, and incidence of cardiac arrhythmias. RESULTS: A total of 39 patients encompassing 107 IV chlorpromazine administrations were included. The median dose was 25 mg. Median vital signs prior to infusion were SBP 129 mm Hg, HR 90 beats/minute, and MAP 88 mm Hg. Over the subsequent 4 hours, SBP and HR did not change significantly (P = .83 and P = .10, respectively). Mean arterial pressure decreased from a median of 88 to 83 mm Hg (P = .04). There were no significant changes in vasopressor requirements, adjunct sedative medication requirements, or achievement of RASS goal. No patients developed symptomatic cardiac arrhythmias. CONCLUSION: In our small retrospective study, the use of IV chlorpromazine at routine doses did not result in clinically significant hemodynamic changes when infused at a rate of 1 mg/min. Intravenous chlorpromazine may be considered as a potential treatment option for agitation in ICU patients with appropriate monitoring.

Ruxolitinib for secondary hemophagocytic lymphohistiocytosis: First case report.

Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder resulting in hyper-activation of inflammatory cytokines. If left untreated, the uncontrolled inflammatory response can lead to significant tissue injury and potentially life-threatening multi-organ dysfunction. Conventional immunosuppressive agents are available for the management of HLH, including dexamethasone, cyclosporine, and etoposide; however, patients may not respond to these therapies. Clinicians may turn toward alternative pharmacologic agents that likely have less clinical evidence. We describe a case of secondary HLH that did not respond favorably to conventional treatments. Serum inflammatory markers continued to rise significantly with clinical deterioration and worsening pancytopenia. The severe thrombocytopenia and neutropenia were deemed to have contributed to a spontaneous subdural hematoma and candidemia, respectively. Ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor, was then utilized as a novel salvage therapy based on available in vivo murine data at the time. Following initiation, there was improvement seen in several disease markers, including serum ferritin, lactate dehydrogenase, fibrinogen, and liver function tests. However, the pancytopenia did not show signs of recovery. The patient ultimately expired after 7days of ruxolitinib treatment. It is unclear if the improvement in disease markers was attributed to JAK inhibition alone. However, this experience combined with the positive in vivo murine data suggests that ruxolitinib may serve as a potential treatment option for HLH, pending the release of more robust data. To our knowledge, this is the first human case report describing the use of ruxolitinib for HLH. Future studies are warranted to determine the role of ruxolitinib in this setting.

Impact of a Pharmacist-Driven Prothrombin Complex Concentrate Protocol on Time to Administration in Patients with Warfarin-associated Intracranial Hemorrhage.

INTRODUCTION: Advancements in the treatment of warfarin-associated intracranial hemorrhage (ICH) include the use of four-factor prothrombin complex concentrate (4F-PCC), which has demonstrated more rapid reversal of the international normalized ratio (INR) when compared with fresh frozen plasma. A pharmacist-driven protocol for 4F-PCC was implemented within our institution, which allows for pharmacist approval of 4F-PCC in patients diagnosed with warfarin-associated ICH and an INR ≥2. The pharmacist is responsible for determining the appropriate dose of 4F-PCC, preparation, bedside delivery, and order entry into the electronic medical record. Prior to implementation of the new protocol, the blood bank was responsible for 4F-PCC approval, dosing, product preparation, and arranging delivery with emergency department (ED) staff. The purpose of this study was to evaluate the impact of a pharmacist-driven protocol on time to 4F-PCC administration in warfarin-associated ICH. METHODS: We performed a retrospective review of consecutive patients who received 4F-PCC in a single ED from September 2015 through February 2017. Patients ≥18 years old were eligible for inclusion based on three criteria: confirmed diagnosis of ICH; confirmed warfarin use; and INR ≥2. Secondary outcomes included dose of 4F-PCC in concordance with INR and weight-based dosing recommendations and hospital protocol, as well as concomitant intravenous vitamin K administration. RESULTS: A total of 48 patients met inclusion criteria for the study with 24 patients in each protocol group. The median time to administration of 4F-PCC in the pharmacist-driven protocol group was 35 minutes (interquartile range [IQR] [25-62]; range, 11-133) compared with 70 minutes (IQR [34-89]; range, 14-244) in the pre-protocol group (p=0.034). We saw no differences for appropriate 4F-PCC dosing based on INR and patient weight between the two groups. CONCLUSION: Implementation of a pharmacist-driven protocol for 4F-PCC in the ED at our institution significantly reduced time to administration in patients presenting with warfarin-associated ICH.

Nimodipine for the treatment of otolaryngic indications.

PURPOSE: The uses of nimodipine for otolaryngic indications are reviewed, and recommendations for its use in clinical practice are provided. SUMMARY: Nimodipine is currently indicated for the improvement of neurologic outcomes in adult patients with aneurysmal subarachnoid hemorrhage (aSAH). However, other oral and i.v. calcium channel blockers have not exhibited the same beneficial effects in patients with aSAH, leading clinicians to believe that nimodipine possesses unique neuroprotective effects in addition to its calcium channel-blocking and vasodilatory properties. Consequently, clinical investigations of nimodipine have been conducted for cochlear and facial nerve preservation after vestibular schwannoma (VS) surgery, symptomatic management of Ménière's disease and peripheral vertigo, and recovery of vocal cord paralysis after laryngeal nerve injury. Three prospective randomized studies have investigated nimodipine for hearing and/or nerve preservation in patients undergoing VS resection, the results of which have suggested a potential benefit of initiating nimodipine during the perioperative period. Several studies of Ménière's disease and/or peripheral vertigo have reported improved symptom control with nimodipine. For vocal fold paralysis associated with recurrent laryngeal nerve (RLN) injury, nimodipine may increase the recovery rate based on the results of 1 nonrandomized prospective study that used nimodipine in a protocolized manner. One small pilot study found that nimodipine improved facial nerve function after maxillofacial surgery. CONCLUSION: Due to its proposed vasoactive and neuroprotective effects, nimodipine may play a role in the treatment of a number of otolaryngic pathologies including VS, Ménière's disease, peripheral vertigo, RLN injury, and facial weakness after maxillofacial surgery. Small studies have shown improved symptom control and recovery after surgery. Since all of the aforementioned indications are still considered off label, clinicians and patients should collaboratively assess the risks and benefits before initiating treatment.

Prospective evaluation of a continuous infusion vancomycin dosing nomogram in critically ill patients undergoing continuous venovenous haemofiltration.

OBJECTIVES: The most optimal method of attaining therapeutic vancomycin concentrations during continuous venovenous haemofiltration (CVVH) remains unclear. Studies have shown continuous infusion vancomycin (CIV) achieves target concentrations more rapidly and consistently when compared with intermittent infusion. Positive correlations between CVVH intensity and vancomycin clearance (CLvanc) have been noted. This study is the first to evaluate a CIV regimen in patients undergoing CVVH that incorporates weight-based CVVH intensity (mL/kg/h) into the dosing nomogram. METHODS: This was a prospective, observational study of patients undergoing CVVH and receiving CIV based on the nomogram. The primary outcome was achievement of a therapeutic vancomycin concentration (15-25 mg/L) at 24 h. Secondary outcomes included the achievement of therapeutic concentrations at 48 and 72 h. RESULTS: The nomogram was analysed in 52 critically ill adults. Vancomycin concentrations were therapeutic in 43/52 patients (82.7%) at 24 h. Of the nine patients who were not therapeutic at 24 h, seven were supratherapeutic and two were subtherapeutic. The mean (SD) concentration was 20.1 (4.2) mg/L at 24 h, 20.7 (3.7) mg/L at 48 h and 21.9 (3.5) mg/L at 72 h. Patients with CVVH intensity >20 mL/kg/h experienced higher CLvanc at 24 h compared with patients with CVVH intensity <20 mL/kg/h (3.1 versus 2.6 L/h; P = 0.013). CONCLUSIONS: By incorporating CVVH intensity into the CIV dosing nomogram, the majority of patients achieved therapeutic concentrations at 24 h and maintained them within range at 48 and 72 h. Additional studies are required to validate this nomogram before widespread implementation may be considered.

Dynamic Interplay of Pharmacy Learners During a Solid Organ Transplantation Learning Experience.

Institutions with established clinical pharmacy services have the ability to offer focused patient care learning experiences, often led by a clinical specialist, for pharmacy residents and pharmacy students. Since all parties are continually involved in professional development and lifelong learning, the aforementioned groups can all be considered "pharmacy learners." By utilizing the dynamic interplay and collaboration between pharmacy learners through direct and nondirect patient care activities, experiential and educational opportunities may be improved and enhanced for each learner. A tiered learning approach engages individuals in areas such as direct patient care, patient education, presentations, research projects, career development, and the feedback process. We describe our experience during a solid organ transplantation learning experience using a layered learning practice model that included a clinical pharmacy specialist, a postgraduate year 2 specialty pharmacy resident, a postgraduate year 1 pharmacy resident, and a pharmacy student.

Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies.

In patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis. For those on dabigatran, the highest quality data available for reversal are for idarucizumab, although it is not yet clear whether patients derive clinical benefit from this reversal. In the absence or failure of idarucizumab, activated prothrombin complex concentrate (aPCC) is recommended. For those on factor Xa inhibitors, the ideal reversal agent is not clear. Many providers use 4F-PCC or aPCC, but more specific agents are in clinical trials and may soon be available. In addition, the half-lives of the non-vitamin K antagonists are relatively short compared with warfarin, and so some patients may not have a clinically relevant coagulopathy at the time of presentation. Overall, the optimal reversal agent, when one is required, is a function of which anticoagulant the patient is taking.

Formation of a Citywide Pharmacy Residents' Collaborative Committee.

Pharmacy residents undergo rigorous training to become skillful and knowledgeable independent practitioners. In addition to delivering direct clinical and operational pharmacy services, residents also participate in various administrative, educational, and scholarly activities as part of their residency experience. Throughout their training, residents may rely on individuals within their network for professional, personal, and emotional support, including residency program directors, preceptors, and co-residents from their respective institutions. Residents from nearby institutions can also serve as a vital resource. Throughout the nation, there are numerous pharmacy residency programs located within the same city or region. Fostering collaboration and relationships between residents from neighboring institutions may provide a support network to augment their training and cultivate an environment to promote work-life balance. We describe our 2-year experience in the formation of a citywide "Pharmacy Residents' Collaborative Committee."

Argatroban for Heparin-Induced Thrombocytopenia during Venovenous Extracorporeal Membrane Oxygenation with Continuous Venovenous Hemofiltration.

Patients receiving extracorporeal membrane oxygenation (ECMO) are at risk of circuit thrombosis due to constant contact between blood and the extracorporeal components. Unfractionated heparin has traditionally been used in this setting as a systemic form of anticoagulation to prevent thrombosis of the circuit. However, if a patient develops heparin-induced thrombocytopenia (HIT), an alternative anticoagulant would be required while the patient is maintained on ECMO. Unfortunately, the pharmacokinetic changes induced by ECMO and critical illness may potentially affect optimal drug dosing. In addition, other modalities, such as continuous renal replacement therapy, may further complicate dosing strategies. We report the case of a 27-year-old man with severe acute respiratory distress syndrome who developed HIT while on venovenous ECMO with continuous venovenous hemofiltration. We describe the successful use of an argatroban infusion in this setting at much higher doses than what has previously been reported in the adult literature.

Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation.

PURPOSE: Previous trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria. METHODS: This was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed. RESULTS: Ninety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K. CONCLUSIONS: 4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.