Benjamin Hohlfelder

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism : The SEATTLE II Study

OBJECTIVES This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

Anticoagulation-associated Adverse Drug Events

PURPOSE Anticoagulant drugs are among the most common medications that cause adverse drug events (ADEs) in hospitalized patients. We performed a 5-year retrospective study at Brigham and Womens Hospital to determine clinical characteristics, types, root causes, and outcomes of anticoagulant-associated ADEs. METHODS We reviewed all inpatient anticoagulant-associated ADEs, including adverse drug reactions (ADRs) and medication errors, reported at Brigham and Womens Hospital through the Safety Reporting System from May 2004 to May 2009. We also collected data about the cost associated with hospitalizations in which ADRs occurred. RESULTS Of 463 anticoagulant-associated ADEs, 226 were medication errors (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR. Seventy percent of anticoagulant-associated ADEs were potentially preventable. Transcription errors (48%) were the most frequent root cause of anticoagulant-associated medication errors, while medication errors (40%) were a common root cause of anticoagulant-associated ADRs. Death within 30 days of anticoagulant-associated ADEs occurred in 11% of patients. After an anticoagulant-associated ADR, most hospitalization expenditures were attributable to nursing costs (mean

Patient education program for venous thromboembolism prevention in hospitalized patients.

33,189 per ADR), followed by pharmacy costs (mean

Venous Thromboembolism in Hospitalized Patients With Active Cancer

7451 per ADR). CONCLUSION Most anticoagulant-associated ADEs among inpatients result from medication errors and are, therefore, potentially preventable. We observed an elevated 30-day mortality rate among patients who suffered an anticoagulant-associated ADE and high hospitalization costs following ADRs. Further quality improvement efforts to reduce anticoagulant-associated medication errors are warranted to improve patient safety and decrease health care expenditures.

Evaluation of sedatives, analgesics, and neuromuscular blocking agents in adults receiving extracorporeal membrane oxygenation

PURPOSE Up to 15% of clinician-ordered doses of injectable pharmacological prophylaxis to prevent venous thromboembolism are not administered. Patient refusal accounts for nearly 50% of these omitted doses. We conducted a prospective cohort study to determine whether a patient education program would improve medication adherence to clinician-ordered injectable prophylactic anticoagulation. METHODS We identified 528 hospitalized patients ordered to receive injectable pharmacological venous thromboembolism prophylaxis. We evaluated the impact of pharmacist-led patient education sessions on medication adherence (defined as the ratio of doses administered to doses scheduled) compared with our historical cohort. RESULTS Individualized patient education sessions were conducted within 24 hours of the initial order for prophylactic anticoagulation in 99% of patients. Adherence to clinician-ordered pharmacological venous thromboembolism prophylaxis was higher after the patient education program than in our historical cohort (94.4% vs 89.9%, P <.0001). The proportion of patients receiving 100% of scheduled doses of injectable pharmacological venous thromboembolism prophylaxis was higher after our novel patient education program than in our historical cohort (73.7% vs 62.4%, P=.001). Patient refusal as a reason for omitted doses was less frequent after the patient education program (29.3% vs 43.7%, P=.001). CONCLUSION Pharmacist-led individualized patient education sessions were associated with higher medication adherence to clinician-ordered injectable pharmacological venous thromboembolism prophylaxis and a reduction in patient refusal as a reason for omitted doses. A randomized controlled trial to evaluate the impact of a patient education program on medication adherence to pharmacological venous thromboembolism prophylaxis is warranted.

Safety of Propofol for Oxygenator Exchange in Extracorporeal Membrane Oxygenation

Venous thromboembolism (VTE) is a common complication of cancer and chemotherapy. We evaluated the baseline clinical characteristics, thromboprophylaxis patterns, frequency and timing of VTE, and clinical outcomes in 1000 adult hospitalized patients with active cancer. Overall, symptomatic VTE occurred in 5.4% of hospitalized patients with cancer. The VTE occurred in 2.3% of patients with cancer during hospitalization and in 3.4% between hospital discharge and day 90. Few (13.9%) hospitalized patients with cancer received extended duration pharmacological prophylaxis after hospital discharge. Cancer was the most frequent known cause of death in both the groups. In conclusion, VTE was common in hospitalized patients with cancer, especially after discharge. Inhospital death and death between discharge and day 90 were frequent in hospitalized patients with cancer who developed VTE.

Development of a Predictive Nomogram for the Change in PT/INR Upon Discontinuation of Bivalirudin as a Bridge to Warfarin

Purpose: The objective of this study was to evaluate the use of sedative, analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing extracorporeal membrane oxygenation (ECMO) support. Materials and methods: This was a 2‐year, prospective, observational study of adult intensive care unit patients on ECMO support for more than 48 hours. Results: We analyzed 32 patients, including 15 receiving VA (venoarterial) ECMO and 17 VV (venovenous) ECMO. The median daily dose of benzodiazepines (midazolam equivalents) was 24 mg, and the median daily dose of opioids (fentanyl equivalents) was 3875 &mgr;g. There was a moderate negative correlation between the day of ECMO and the median daily benzodiazepine dose (r = −0.5515) and a very weak negative correlation for the median daily opioid dose (r = −0.0053). On average, patients were sedated to Richmond Agitation Sedation Scale scores between 0 and −1. Continuous infusions of opioids, benzodiazepines, propofol, dexmedetomidine, and NMBAs were administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%) ECMO days, respectively. Patients in the VA arm received a continuous infusion opioid (96.4% vs 81.6% days; P < .001) and benzodiazepine (58.2% vs 37.0% days; P < .001) more frequently. Conclusions: Patients received relatively low doses of sedatives and analgesics while at a light level of sedation on average. Patients rarely required neuromuscular blockade.

Implementation of a Prolonged Infusion Guideline for Time-Dependent Antimicrobial Agents at a Tertiary Academic Medical Center.

The purpose of this analysis is to describe the safety of propofol administration in adult extracorporeal membrane oxygenation (ECMO) patients. We performed a prospective cohort analysis of patients using ECMO at Brigham and Womens Hospital between February 2013 and October 2015. Patients were included if they used ECMO for at least 48 hours. The major end-point of the analysis was the median oxygenator lifespan. Oxygenator exchanges were analyzed by the number of patients requiring an oxygenator exchange and the number of oxygenator exchanges per ECMO day. A priori analysis was performed by comparing the outcomes between patients who did and did not receive propofol during their ECMO course. During the study, 43 patients were included in the analysis. Sixteen patients used propofol during their ECMO course. There were 12 oxygenator exchanges during therapy. Oxygenator exchange occurred on 1.8% of ECMO days. The median oxygenator lifespan was 7 days. Patients who used propofol had a significantly longer oxygenator lifespan (p = 0.02). Among patients who received propofol, patients who required oxygenator exchange used a significantly lower median daily dose of propofol (p < 0.001). The use of propofol appears safe in ECMO with regards to oxygenator viability. Contrary to expected, oxygenator lifespan was significantly longer among patients who received propofol.

Handbook for Venous Thromboembolism

Appropriate timing of bivalirudin discontinuation as a bridge to warfarin is complicated, as bivalirudin may cause a falsely prolonged international normalized ratio (INR). The purpose was to evaluate patient and medication characteristics associated with differences in INR prolongation caused by bivalirudin. Adult patients receiving bivalirudin as a bridge to warfarin in 2014 were retrospectively evaluated. Patients were excluded if they had known thrombophilia or inappropriate INR monitoring after discontinuation of bivalirudin. Data recorded included indication for bivalirudin use, bivalirudin dosing, and coagulation assays. Univariate analysis was performed to determine variables associated with a larger change in INR when discontinuing bivalirudin. Variables with P < .3 were included in multivariate analysis. In total, 50 patient admissions were included in the analysis. Patients with ventricular assist devices represented the majority of the patient population (74%). The most common INR goals were 2.0 to 3.0 and 2.5 to 3.5. The mean initial weight-based bivalirudin rate was 0.076 mg/kg/h, and the mean increase in INR when starting bivalirudin was 0.6. The mean final weight-based bivalirudin rate was 0.13 mg/kg/h, and the mean change in INR after stopping bivalirudin was 0.8. On multivariate analysis, factors associated with a larger change in INR after stopping bivalirudin included higher serum creatinine (P = .033), greater change in INR after initiation of bivalirudin (P = .028), and higher final bivalirudin rate (P < .001). The change in INR when starting or stopping bivalirudin appears to be patient specific and dose related. A nomogram was developed to predict the ideal timing of bivalirudin discontinuation. Prospective evaluation of the nomogram is under way.

Improvements in a program to convert i.v. to oral medications at an academic medical center.

Administration of time-dependent beta-lactam antibiotic as a prolonged infusion may maximize the pharmacodynamic target of time above the minimum inhibitory concentration. We describe the implementation of a prolonged infusion at a tertiary academic medical center, and a 1-year compliance analysis with the guideline. After performing a thorough literature search, a guideline was developed by members of the Department of Infectious Diseases and Department of Pharmacy. Approval and endorsement of the guideline was obtained by the Antimicrobial Subcommittee and Pharmacy and Therapeutics Committee. Physical champions were instrumental in the implementation of the guideline institution-wide. We then performed a 1-year retrospective analysis of guideline compliance from January 1, 2011 to December 31, 2011. Noncompliant administrations were obtained from smart infusion pumps. The total number of doses administered was taken from pharmacy information resources. In total, nearly 85,000 time-dependent doses were administered. Compliance with the prolonged infusion guideline was 89%. Rates of compliance did not significantly differ between medications (P = 0.555). Obtaining support from key stakeholders in collateral services and institutional leadership was vital for the success of this guideline. Compliance with the guideline 1 year after implementation was high. Implementation of a prolonged infusion guideline is feasible with institutional support and motivation.