Cassie A. Barton

Hemopericardium in a Patient Treated with Dabigatran Etexilate

Dabigatran etexilate is a new oral anticoagulant used for the prevention of systemic thromboembolism in patients with atrial fibrillation. Acute bleeding episodes are known to occur with dabigatran etexilate therapy; however, only a few case reports in the literature describe such events. We describe a 70‐year‐old man treated with dabigatran etexilate for newly diagnosed, nonvalvular atrial fibrillation who developed a large hemopericardium that appeared to be temporally related to dabigatran etexilate administration. One month after starting the drug, an incidental finding of a small pericardial effusion was found on echocardiography. One month later, the patient came to his pulmonologists office complaining of shortness of breath; a large pericardial effusion was found on a noncontrast computed tomographic scan, and the patient was admitted to the hospital. Laboratory monitoring of his coagulation status was limited due to the lack of assays available to directly monitor the therapeutic effects of dabigatran. The internal laboratory was able to perform a dilute thrombin time (DTT) test as part of a quality improvement project aiming to validate an assay for monitoring patients receiving dabigatran therapy. A DTT was therefore performed in conjunction with routine coagulation assays to evaluate the patients coagulation status. After pericardiocentesis, the patient recovered without incident and was discharged without anticoagulant therapy. Although the Naranjo adverse reaction probability scale only indicated a possible relationship (score of 1) between the patients development of hemopericardium and dabigatran etexilate therapy, investigation into the patients clinical course, comorbidities, and laboratory results led us to conclude that dabigatran etexilate was responsible for the hemopericardium. To our knowledge, this report is the first to describe a case of potentially life‐threatening pericardial bleeding that was temporally related to starting dabigatran etexilate therapy. Although we found that the DTT was a viable method of monitoring coagulation status in a patient receiving dabigatran etexilate therapy, the assay lacks approval by the United States Food and Drug Administration, which limits its clinical utility and widespread use at this time. Clinicians should be aware of the potential for life‐threatening bleeding with use of this agent and the difficulty associated with monitoring and reversing this therapy in the setting of acute bleeding.

Risk of thromboembolic events after protocolized warfarin reversal with 3-factor PCC and factor VIIa.

Bleeding events and life-threatening hemorrhage are the most feared complications of warfarin therapy. Prompt anticoagulant reversal aimed at replacement of vitamin K-dependent clotting factors is essential to promote hemostasis. A retrospective cohort study of warfarin-treated patients experiencing a life-threatening hemorrhage treated with an institution-specific warfarin reversal protocol (postimplementation group) and those who received the prior standard of care (preimplementation group) was performed. The reversal protocol included vitamin K, 3-factor prothrombin complex concentrate, and recombinant factor VIIa. Demographic and clinical information, anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. A total of 227 patients were included in final analysis, 109 in the preimplementation group and 118 in the postimplementation group. Baseline patient characteristics were similar in both groups, with the exception of higher average Sequential Organ Failure Assessment scores in the postimplementation group (P = .0005). The most common indication for anticoagulation reversal was intraparenchymal hemorrhage. Prereversal international normalized ratios (INRs) were similar in both groups. Attainment of INR normalization to less than 1.4 was higher, and rebound INR was lower in the postimplementation group (P < .0001; P = .0013). Thromboembolic complications were significantly higher in the postimplementation group (P = .003). Elevated baseline Sequential Organ Failure Assessment score and mechanical valve as an indication for anticoagulation were independently associated with thrombotic complications (P = .005). A warfarin reversal protocol consisting of 3-factor prothrombin complex concentrate, recombinant factor VIIa, and vitamin K more consistently normalized INR values to less than 1.4 as compared to the prior standard of care in a diverse patient population. This success came at the cost of a 2-fold increase in risk of thromboembolic complications.

Compliance with the Eastern Association for the Surgery of Trauma guidelines for prophylactic antibiotics after open extremity fracture

Context: Prophylactic antibiotics, paired with wound care and surgical intervention, is considered the standard of care for patients with open fracture. Guidelines from the Eastern Association for the Surgery of Trauma (EAST) recommend specific prophylactic antimicrobial therapy based on the type of open fracture. Aims: We quantified adherence to EAST guideline recommendations and documented the incidence of infection in patients with open fracture. Settings and Design: A retrospective, observational study of all patients with open fracture admitted to our facility from January 2004 to December 2008 was conducted. Materials and Methods: Patients were divided into compliant and noncompliant groups according to the EAST guideline recommendations. Compliance was defined as an appropriate spectrum of therapy for guideline suggested duration. We assessed for surgical and non-surgical site infections, and morbidity outcomes. Statistical Analysis: Nominal data were explored using summary measures. Continuous variables were compared using the Student t-test or the Mann–Whitney U-test. Dichotomous data were compared using χ2 statistic or Fishers exact test. Results: The final analysis included 214 patients. Prophylactic antibiotics were guideline compliant in 28.5% of patients, and ranged from 10.0% in type 3b fractures to 52.7% in type 1 fractures. The most common reason for non-compliance was the use of guideline recommended coverage that exceeded the suggested duration (71.2%). Patients who received non-compliant therapy required prolonged hospital lengths of stay (6 vs. 3 days, P = 0.0001). The overall incidence of infection was similar regardless of guideline compliance (17.0% vs. 11.5%, P = 0.313). Conclusions: Prophylactic antibiotics for open fracture frequently exceeded guideline recommendations in duration and spectrum of coverage, especially in more severe fracture types. Non-compliance with EAST recommendations was associated with increased in-hospital morbidity.

Original ContributionRisk of thromboembolic events after protocolized warfarin reversal with 3-factor PCC and factor VIIa☆☆☆

Bleeding events and life-threatening hemorrhage are the most feared complications of warfarin therapy. Prompt anticoagulant reversal aimed at replacement of vitamin K-dependent clotting factors is essential to promote hemostasis. A retrospective cohort study of warfarin-treated patients experiencing a life-threatening hemorrhage treated with an institution-specific warfarin reversal protocol (postimplementation group) and those who received the prior standard of care (preimplementation group) was performed. The reversal protocol included vitamin K, 3-factor prothrombin complex concentrate, and recombinant factor VIIa. Demographic and clinical information, anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. A total of 227 patients were included in final analysis, 109 in the preimplementation group and 118 in the postimplementation group. Baseline patient characteristics were similar in both groups, with the exception of higher average Sequential Organ Failure Assessment scores in the postimplementation group (P = .0005). The most common indication for anticoagulation reversal was intraparenchymal hemorrhage. Prereversal international normalized ratios (INRs) were similar in both groups. Attainment of INR normalization to less than 1.4 was higher, and rebound INR was lower in the postimplementation group (P < .0001; P = .0013). Thromboembolic complications were significantly higher in the postimplementation group (P = .003). Elevated baseline Sequential Organ Failure Assessment score and mechanical valve as an indication for anticoagulation were independently associated with thrombotic complications (P = .005). A warfarin reversal protocol consisting of 3-factor prothrombin complex concentrate, recombinant factor VIIa, and vitamin K more consistently normalized INR values to less than 1.4 as compared to the prior standard of care in a diverse patient population. This success came at the cost of a 2-fold increase in risk of thromboembolic complications.

Anticoagulation management around percutaneous bedside procedures: is adjustment required?

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) and percutaneous dilatational tracheostomy (PDT) are frequently performed bedside in the intensive care unit. Critically ill patients frequently require anticoagulant (AC) and antiplatelet (AP) therapies for myriad indications. There are no societal guidelines proffering strategies to manage AC/AP therapies periprocedurally for bedside PEG or PDT. The aim of this study is to evaluate the management of AC/AP therapies around PEG/PDT, assess periprocedural bleeding complications, and identify risk factors associated with bleeding. METHODS: A retrospective, observational study of all adult patients admitted from October 2004 to December 2009 receiving a bedside PEG or PDT was conducted. Patients were identified by procedure codes via an in-hospital database. A medical record review was performed for each included patient. RESULTS: Four hundred fifteen patients were included, with 187 PEGs and 352 PDTs being performed. Prophylactic anticoagulation was held for approximately one dose before and two doses or less after the procedure. There was wide variation in patterns of holding therapy in patients receiving anticoagulation via continuous infusion. There were 19 recorded minor bleeding events, 1 (0.5%) with PEG and 18 (5.1%) with PDT, with no hemorrhagic events. No association was found between international normalized ratio, prothrombin time, or activated partial thromboplastin time values and bleed risk (p = 0.853, 0.689, and 0.440, respectively). Platelet count was significantly lower in patients with a bleeding event (p = 0.006). CONCLUSIONS: We found that while practice patterns were quite consistent in regard to the management of prophylactic anticoagulation, it varied widely in patients receiving therapeutic anticoagulation. It seems that prophylactic anticoagulation use did not affect bleed risk with PEG/PDT. LEVEL OF EVIDENCE: II, therapeutic study.

Antimicrobial prophylaxis during Hirudo medicinalis therapy: a multicenter study.

BACKGROUND Medicinal leeches (Hirudo medicinalis) are indicated for salvage of tissue flaps, grafts, or replants when venous congestion threatens tissue viability. The purpose of this study was to evaluate the efficacy of prophylactic antimicrobial agents in patients who received medicinal leech therapy. MATERIALS AND METHODS A multicenter retrospective cohort study of all adult patients between January 1, 2010, and February 28, 2013, who received medicinal leech therapy was conducted. RESULTS Antimicrobial prophylaxis was documented in 54 (91.5%) of the included patients, ciprofloxacin, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, and ceftriaxone in 33 (61.1%), 18 (33.3%), 2 (3.7%), and 2 (3.7%) patients, respectively. Surgical site infection (SSI) was found in seven (11.9%) patients, all of whom received antimicrobial prophylaxis. Aeromonas spp. was isolated in four infections, and all isolates were resistant to the chosen prophylactic agent. The SSI incidence was similar between antimicrobial prophylaxis agents. CONCLUSION Trimethoprim-sulfamethoxazole and ciprofloxacin appear equally effective at preventing leech-associated infections.

Treatment of Coagulopathy Related to Hepatic Insufficiency.

Objectives:To provide a concise review of the medical management of coagulopathy related to hepatic insufficiency. This review will focus on prevention and management of bleeding episodes in patients with hepatic insufficiency. The treatment and prevention of thromboembolic complications will also be addressed. Data Sources:Electronic search of PubMed database using relevant search terms, including hepatic coagulopathy, hemorrhage, liver diseases, blood coagulation disorders, blood transfusion, disseminated intravascular coagulation, and liver failure. Subsequent searches were done on specific issues. Study Selection:Articles considered include original articles, review articles, guidelines, consensus statements, and conference proceedings. Data Extraction:A detailed review of scientific, peer-reviewed data was performed. Relevant publications were included and summarized. Data Synthesis:Available evidence is used to describe and summarize currently available tests of hemostasis, utilization of prohemostatic agents, transfusion strategies, use of prophylactic anticoagulation and treatment of thromboembolic events in patients with hepatic insufficiency. Conclusions:Dynamic changes to hemostasis occur in patients with hepatic insufficiency. Routine laboratory tests of hemostasis are unable to reflect these changes and should not be used exclusively to evaluate coagulopathy. Newer testing methods are available to provide data on the entire spectrum of clotting but are not validated in acute bleeding. Prohemostatic agents utilized to prevent bleeding should only be considered when the risk of bleeding outweighs the risk of thrombotic complications. Restrictive transfusion strategies may avoid exacerbation of acute bleeding. Prophylaxis against and treatment of thromboembolic events are necessary and should consider patient specific factors.

Successful Treatment of a Massive Metoprolol Overdose Using Intravenous Lipid Emulsion and Hyperinsulinemia/Euglycemia Therapy

Adrenergic β‐antagonists, commonly known as β‐blockers, are prescribed for many indications including hypertension, heart failure, arrhythmias, and migraines. Metoprolol is a moderately lipophilic β‐blocker that in overdose causes direct myocardial depression leading to bradycardia, hypotension, and the potential for cardiovascular collapse. We describe the case of a 59‐year‐old man who intentionally ingested ~7.5 g of metoprolol tartrate. Initial treatment of bradycardia and hypotension included glucagon, atropine, dopamine, and norepinephrine. Despite these treatment modalities, the patient developed cardiac arrest. Intravenous lipid emulsion (ILE) and hyperinsulinemia/euglycemia (HIE) therapies were initiated during advanced cardiac life support and were immediately followed by return of spontaneous circulation. Further treatment included gastric lavage, activated charcoal, continued vasopressor therapy, and a repeat bolus of ILE. The patient was weaned off vasoactive infusions and was extubated within 24 hours. HIE therapy was continued for 36 hours after metoprolol ingestion. A urine β‐blocker panel using mass spectrometry revealed a metoprolol concentration of 120 ng/ml and the absence of other β‐blocking agents. To date, no clear treatment guidelines are available for β‐blocker overdose, and the response to toxic concentrations is highly variable. In this case of a life‐threatening single‐agent metoprolol overdose, the patient was successfully treated with HIE and ILE therapy. Due to the increasing frequency with which ILE and HIE are being used for the treatment of β‐blocker overdose, clinicians should be aware of their dosing strategies and indications.

Achieving ventricular rate control using metoprolol in β-blocker–naive patients vs patients on chronic β-blocker therapy

STUDY OBJECTIVE The objective of the study is to evaluate the difference in ventricular rate control using an intravenous (IV) metoprolol regimen commonly used in clinical practice in patients receiving chronic β-blocker therapy compared to patients considered β-blocker naive admitted to the emergency department (ED) for atrial fibrillation (AF) with rapid ventricular rate. METHODS A single-center retrospective cohort study of adult ED patients who were admitted with a rapid ventricular rate of 120 beats per minute (bpm) or greater and treated with IV metoprolol was performed. Rate control was defined as either a decrease in ventricular rate to less than 100 bpm or a 20% decrease in heart rate to less than 120 bpm after metoprolol administration. Patient demographics, differences in length of stay, and adverse events were recorded. RESULTS A total of 398 patients were included in the study, with 79.4% (n=316) receiving chronic β-blocker therapy. Patients considered to be β-blocker naive were more likely to achieve successful rate control with IV metoprolol compared to patients on chronic β-blocker therapy (56.1% vs 42.4%; P=.03). β-Blocker-naive status was associated with a shorter length of stay in comparison to patients receiving chronic β-blocker therapy (1.79 vs 2.64 days; P<.01). CONCLUSION Intravenous metoprolol for the treatment of atrial fibrillation with rapid ventricular rate was associated with a higher treatment response in patients considered β-blocker naive compared to patients receiving chronic β-blocker therapy.

Protocolized warfarin reversal with 4-factor prothrombin complex concentrate versus 3-factor prothrombin complex concentrate with recombinant factor VIIa

INTRODUCTION Life-threatening bleeding can complicate warfarin therapy. Rapid anticoagulant reversal via replacement of vitamin-K dependent clotting factors is essential for hemostasis. We compare two methods of rapid factor replacement for warfarin reversal. METHODS A retrospective cohort study of warfarin-treated patients experiencing life-threatening bleeding who received a reversal protocol comprised of 4F PCC or 3F PCC and rFVIIa was performed. Demographic, clinical and anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. RESULTS 195 patients were included in final analysis. While baseline demographics were similar between groups, the 3F-PCC group had a longer ICU LOS and higher in-hospital mortality (p < .01, .01). Pre-reversal INR was similar between both groups, but post-reversal INR was significantly lower in the 3F-PCC group, 0.8 versus 1.3 (p < .01). Significantly more patients experienced thromboembolic complications in the 3F-PCC group than the 4F-PCC group (p < .01). Receipt of rFVIIa was significantly associated with thromboembolic complications. DISCUSSION A 4F PCC reversal strategy is efficacious in INR reversal and provides lower thromboembolic risk as compared to 3F PCC with rFVIIa.