Hydroxocobalamin Versus Methylene Blue for the Treatment of Vasoplegic Shock Associated With Cardiopulmonary Bypass.

OBJECTIVES: To compare changes in vasopressor requirements and hemodynamic responses after hydroxocobalamin or methylene blue administration for vasoplegic shock (VS). DESIGN: Retrospective cohort analysis. SETTING: Single-center, academic medical center. PATIENTS: Cardiothoracic surgery adult patients. INTERVENTIONS: Hydroxocobalamin or methylene blue. MEASUREMENTS: The primary outcome was a change in vasopressor requirements over the first 24 hours (1, 3, 6, 12, and 24 hours) after hydroxocobalamin or methylene blue initiation. Secondary outcomes included changes in mean arterial pressure (MAP), systemic vascular resistance, and lactate. MAIN RESULTS: A total of 120 adult patients who received hydroxocobalamin (n = 77) or methylene blue (n = 43) were included. Vasopressor requirements at baseline were 0.34 µg/kg/min (95% CI 0.28-0.4) norepinephrine equivalent (NEE) in the hydroxocobalamin group, and 0.59 µg/kg/min (95% CI 0.52-0.66) NEE in the methylene blue group; p < 0.001. Vasopressor requirements decreased significantly at each time point within each group (hour 1 mean [95% CI] NEE, hydroxocobalamin 0.27 µg/kg/min [0.21-0.33]; methylene blue 0.44 µg/kg/min [0.38-0.51]; p < 0.001). The mean MAP at baseline was 65 mmHg (95% CI 63-67) in the hydroxocobalamin group, and 57 mmHg (95% CI 54-59) in the methylene blue group; p < 0.001. The mean MAP increased significantly from baseline at each time point within each group (hour 1 mean [95% CI] hydroxocobalamin 73 mmHg [71-75]; methylene blue 67 mmHg [65-70]; p < 0.001). After adjusting for baseline characteristics, a significantly greater reduction in vasopressor requirements and an increase in MAP were noted in the hydroxocobalamin group compared with the methylene blue group. CONCLUSIONS: Hydroxocobalamin was associated with a greater reduction in vasopressor requirements than methylene blue in treating VS associated with cardiopulmonary bypass.

Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

Association of Methylene Blue Dosing With Hemodynamic Response for the Treatment of Vasoplegia.

OBJECTIVES: To compare the hemodynamic response of methylene blue dosing regimens (bolus v bolus plus infusion) for the treatment of vasoplegia. DESIGN: A retrospective cohort analysis. SETTING: A single-center academic medical center. PARTICIPANTS: Patients who underwent cardiac surgery at Cleveland Clinic and received methylene blue between 2016 and 2019. Patients were excluded from the analysis if methylene blue was initiated >48 hours after surgery, if the cardiac index was <2.0 L/min/m2, or if they returned to the operating room for postoperative hemorrhage. INTERVENTIONS: Methylene blue bolus-only regimens versus bolus plus continuous infusion methylene blue regimens. MEASUREMENTS AND MAIN RESULTS: The primary outcome was vasopressor requirement over 48 hours (1, 3, 6, 12, 24, and 48 hours) after methylene blue initiation. Other hemodynamic outcomes evaluated included the rate of methylene blue response, mean arterial pressure (MAP), and systemic vascular resistance (SVR) values over time. In total, 44 patients were included in the analysis, 33 of whom only received a methylene blue bolus. Vasopressor requirements at baseline were 95 (95% CI: 70-122) µg/min norepinephrine equivalent (NE) in the bolus-only group and 100 (86-130) µg/min in the infusion group. Vasopressor requirements decreased at each time point in both groups and were similar throughout (hour 1 mean [95% CI] NE, bolus 79 [67-91] µg/min v bolus plus infusion 84 [63-104] µg/min; p = 0.71). MAP, SVR, and rates of methylene blue response were similar between groups at all time points. Clinical outcomes also were similar between groups. CONCLUSIONS: The addition of a methylene blue continuous infusion did not significantly improve hemodynamic response. Bolus-only dosing of methylene blue may be sufficient for the treatment of vasoplegia after cardiac surgery.

Determinants of Vancomycin Trough Concentration in Patients Receiving Continuous Veno-Venous Hemodialysis.

BACKGROUND: Vancomycin pharmacokinetics are altered in the critically ill and are further distorted by renal replacement therapy. Limited literature is available evaluating vancomycin dosing in continuous veno-venous hemodialysis (CVVHD). OBJECTIVE: The goal of this analysis was to identify factors that affect vancomycin trough concentration in patients on CVVHD and to determine an appropriate dosing strategy. METHODS: This was a single-center, retrospective cohort study of adult inpatients admitted to the Cleveland Clinic from May 2016-December 2017. Patients in the intensive care unit who received ≥ 2 doses of vancomycin during CVVHD were included. Patients with interruptions of CVVHD inappropriately timed troughs, a change in dialysate rate, and those who received different vancomycin dosages were excluded. Multivariable linear regression including age, sex, weight, Sequential Organ Failure Assessment score, albumin, 24-hour urine output (UOP), dialysate rate, filter type, and vancomycin dose was run to determine predictors of vancomycin concentration. RESULTS: A total of 160 patients were included. The median vancomycin dose was 12.6 mg/kg with a trough of 24.6 mcg/mL. Weight, 24-hour UOP, vancomycin dose (mg/kg), and dialysate rate (mL/kg/h) were all determined to be independent predictors of vancomycin trough level. Patients who received <10 mg/kg doses of vancomycin (N=18) achieved a median trough of 21.5 mcg/mL, with 83% being therapuetic. In patients who received >10 mg/kg (N=142), the median trough was 25.5 mcg/mL, with 47% being therapeutic. CONCLUSION AND RELEVANCE: Vancomycin dose, dialysate rate, UOP, and weight are independently associated with vancomycin trough concentration. In CVVHD patients, vancomycin dosed at 10 mg/kg every 24 hours may be an appropriate recommendation.

A Review of Pulmonary Arterial Hypertension Treatment in Extracorporeal Membrane Oxygenation: A Case Series of Adult Patients.

BACKGROUND: Little data is published describing the use of medications prescribed for pulmonary arterial hypertension (PAH) in patients receiving extracorporeal membrane oxygenation (ECMO). Even though many patients with PAH may require ECMO as a bridge to transplant or recovery, little is reported regarding the use of PAH medications in this setting. METHODS: This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO. RESULTS: Eight PAH patients, 5 of whom were female, ranging in age from 21 to 61 years old, were initiated on ECMO. Veno-arterial (VA) ECMO was used in 4 patients, veno-venous (VV) ECMO and hybrid ECMO configurations in 2 patients respectively. Common indications for ECMO included cardiogenic shock, bridge to transplant, and cardiac arrest. All patients were on intravenous (IV) prostacyclin therapy at baseline. Refractory hypotension was noted in 7 patients of whom 5 patients required downtitration or discontinuation of baseline PAH therapies. Three patients had continuous inhaled epoprostenol added during their time on ECMO. In patients who were decannulated from ECMO, PAH therapies were typically resumed or titrated back to baseline dosages. One patient required no adjustment in PAH therapy while on ECMO. Two patients were not able to be decannulated from ECMO. CONCLUSION: The treatment of critically ill PAH patients is challenging given a variety of factors that could affect PAH drug concentrations. In particular, PAH patients on prostacyclin analogues placed on VA ECMO appear to have pronounced systemic vasodilation requiring vasopressors which is alleviated by temporarily reducing the intravenous prostacyclin dose. Patients should be closely monitored for potential need for rapid titrations in prostacyclin therapy to maintain hemodynamic stability.

Activated Clotting Times Demonstrate Weak Correlation With Heparin Dosing in Adult Extracorporeal Membrane Oxygenation.

BACKGROUND: The optimal monitoring strategy for anticoagulation management in extracorporeal membrane oxygenation (ECMO) remains a clinical controversy. The Extracorporeal Life Support Organization Anticoagulation Guidelines suggest that multiple anticoagulation assays may be needed but do not specify a preferred management strategy. STUDY QUESTION: In adult ECMO patients, which anticoagulation assays demonstrate the highest correlation with unfractionated heparin (UFH) dose requirements? STUDY DESIGN: We performed a retrospective chart review of adult patients cannulated to ECMO between February 2013 and July 2015. MEASURES AND OUTCOMES: The primary outcome was the correlation between activated clotting time (ACT), activated partial thromboplastin time (aPTT), and anti-Xa and UFH dose. Secondary outcomes included correlations between anticoagulation assays. Correlations were calculated for the entire cohort, with subgroup analysis of venoarterial and venovenous ECMO patients. RESULTS: Forty-eight patients were included in the analysis, 26 initially cannulated to venoarterial ECMO and 22 to veno-venous ECMO. The median duration of ECMO therapy was 7 days. Mean UFH requirements were 1149 units/h or 15.3 units/kg/h. Total UFH dose was most correlated with anti-Xa levels (r = 0.467), whereas weight-based heparin dose was most correlated with aPTT (0.405). For correlations between anticoagulation assays, anti-Xa and aPTT were more highly correlated with each other (r = 0.633) compared with ACT. CONCLUSIONS: In adult patients requiring ECMO, anti-Xa and aPTT monitoring were correlated more closely with UFH dosing than ACT.

Antibody-Mediated Rejection Management Following Lung Transplantation.

BACKGROUND: Although antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited. OBJECTIVE: The purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients. METHODS: This single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019. RESULTS: A total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter. CONCLUSION AND RELEVANCE: This represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.

Opioid and sedative requirements in extracorporeal membrane oxygenation patients on hydromorphone versus fentanyl.

BACKGROUND: The extracorporeal membrane oxygenation (ECMO) circuit causes pharmacokinetic alterations of medications which impact drug selection and dosing. Although hydromorphone has a favorable pharmacokinetic profile, it is unclear whether hydromorphone provides better patient-centered benefits compared to fentanyl. The objective of this study is to compare opioid and sedative requirements in ECMO patients started on a fentanyl- versus hydromorphone-based analgesia regimen. METHODS: This was a non-interventional retrospective cohort study. It was conducted at a single center in the cardiovascular intensive care units and cardiac intensive care units. We included venovenous (VV) or venoarterial ECMO patients. Patients who were started on a fentanyl continuous infusion within 24 h of cannulation were compared to patients started on a hydromorphone continuous infusion. RESULTS: A linear mixed effects model was performed to compare doses of opioid, sedative, and propofol between groups over time. We included 28 hydromorphone patients and 53 fentanyl patients, with 85% on VV ECMO. There were no differences between hydromorphone and fentanyl groups in opioid or sedative (including propofol and benzodiazepine) doses for any ECMO day (p value for interaction .63 and .83, respectively). Propofol doses alone, however, were significantly higher in the fentanyl group on ECMO days three, four, and five. CONCLUSIONS: There appear to be no major differences in opioid or sedative requirements whether ECMO patients are initiated on a hydromorphone- or fentanyl-based regimen.

Prescribing Practices of Valproic Acid for Agitation and Delirium in the Intensive Care Unit.

BACKGROUND: Analgesics, sedatives, and antipsychotics are commonly prescribed for agitation and delirium in the intensive care unit (ICU), but their use is limited by adverse effects and lack of efficacy. Valproic acid is an alternative treatment option. OBJECTIVE: The primary objective of this study was to describe valproic acid prescribing in our institution's ICUs when used for agitation or delirium. Measures of effectiveness and safety were also assessed. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study of adult inpatients admitted to the ICU between January 2018 and August 2018. Patients who received valproic acid for the treatment of agitation or delirium for ≥24 hours were included. Prescribing practices were evaluated for dose, frequency, and route of administration. Effectiveness was assessed via agitation and delirium assessment tools and quantity of adjunctive agents used. RESULTS: A total of 80 patients were included, with 35 receiving valproic acid alone and 45 in conjunction with antipsychotics. The most common valproic acid regimen was 250 mg orally 3 times daily. Delirium resolution occurred in 55% of patients: 24 in the valproic acid monotherapy group and 20 in the valproic acid plus antipsychotic group (69% vs 44%; P = 0.03). The incidence of delirium decreased from valproic acid day 0 to day 3 (93% vs 68%; P < 0.01), with no change in agitation (64% vs 63%; P = 0.28). CONCLUSION AND RELEVANCE: Valproic acid is frequently prescribed in agitated, delirious patients at our institution and may have a role in the management of ICU delirium.

Anticoagulation with temporary Impella device in patients with heparin-induced thrombocytopenia: A case series.

The Impella device is a percutaneous ventricular assist devices that requires administration of heparin via a continuous purge solution. Patients on Impella device support may experience hemolysis with accompanying thrombocytopenia generating suspicion for heparin-induced thrombocytopenia (HIT). However, data and recommendations for use of non-heparin anticoagulants with Impella device are lacking. Therefore, we performed a retrospective cohort analysis of patients requiring bivalirudin during Impella device support to describe the safety and efficacy of bivalirudin as an alternative anticoagulant during Impella device support. Nine patients were included in the evaluation which analyzed Impella device purge flow and purge pressure along with bivalirudin dosing requirements, incidence of thrombosis, and incidence of pump failure. All patients had a positive platelet factor-4 IgG ELISA test, and the serotonin release assay was positive in four patients. After initiation of bivalirudin, the median (15th, 85th percentile) nadir purge flow decreased by 76% (5%, 88%) and the median (15th, 85th percentile) peak purge pressure increased by 86% (21%, 143%). At the time of bivalirudin discontinuation, the median final purge flow and pressure were 2.4 mL/h (74% decrease) and 969 mmHg (89% increase), respectively. Zero patients experienced catastrophic pump failure. Adding low concentration bivalirudin to the purge solution along with systemic bivalirudin may be a reasonable approach.

Inpatient Initiation of Oral Treprostinil in an Academic Medical System.

PURPOSE: Clinicians may transition patients on parenteral or inhaled prostacyclins to oral treprostinil for ease of use or to avoid adverse effects related to parenteral therapy. However, few data are available to guide these transitions in inpatients. The purpose of this analysis is to describe the inpatient initiation of oral treprostinil at an academic medical system. METHODS: This is a retrospective cohort analysis of patients newly initiated on oral treprostinil at Cleveland Clinic Heath System from 2015 to 2017. Demographic information regarding pulmonary arterial hypertension (PAH) history and previous PAH therapies were recorded. Outcomes evaluated included doses of oral treprostinil utilized, adverse effects related to therapy, and measures of clinical and functional status before and after the initiation of oral treprostinil. RESULTS: Overall, 29 patients were prescribed oral treprostinil, of which 15 patients were included in the analysis. Common reasons for initiation of oral treprostinil included disease progression (6, 40%) and patient desire (4, 25%). The median duration of transition/initiation of oral treprostinil was 4 days (range, 3-11 days). Median daily dose of oral treprostinil on day 1 of initiation was 2 mg (0.25-4 mg). By day 7, median daily dose was 15 mg (0.75-27.75 mg). Common adverse effects related to therapy were gastrointestinal (7, 47%) and headache (4, 27%). No patients required discontinuation of oral treprostinil due to adverse effects within 90 days of initiation. CONCLUSION: Inpatient initiation/transition to oral treprostinil was relatively well tolerated. Future studies should evaluate clinical outcomes surrounding the transitioning to oral treprostinil.

Alert-based computerized decision support for high-risk hospitalized patients with atrial fibrillation not prescribed anticoagulation: a randomized, controlled trial (AF-ALERT).

AIMS: Despite widely available risk stratification tools, safe and effective anticoagulant options, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is underprescribed. We created and evaluated an alert-based computerized decision support (CDS) strategy to increase anticoagulation prescription in hospitalized AF patients at high risk for stroke. METHODS AND RESULTS: We enrolled 458 patients (CHA2DS2-VASc score ≥1) with AF who were not prescribed anticoagulant therapy and were hospitalized at Brigham and Women's Hospital. Patients were randomly allocated, according to Attending Physician of record, to intervention (alert-based CDS) vs. control (no notification). The primary efficacy outcome was the frequency of anticoagulant prescription. The CDS tool assigned 248 patients to the alert group and 210 to the control group. Patients in the alert group were more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%, P < 0.0001), at discharge (23.8% vs. 12.9%, P = 0.003), and at 90 days (27.7% vs. 17.1%, P = 0.007). The alert reduced the odds of a composite outcome of death, myocardial infarction (MI), cerebrovascular event, and systemic embolic event at 90 days [11.3% vs. 21.9%, P = 0.002; odds ratio (OR) 0.45; 95% confidence interval (CI) 0.27-0.76]. The alert reduced the odds of MI at 90 days by 87% (1.2% vs. 8.6%, P = 0.0002; OR 0.13; 95% CI 0.04-0.45) and cerebrovascular events or systemic embolism at 90 days by 88% (0% vs. 2.4%, P = 0.02; OR 0.12; 95% CI 0.0-0.91). CONCLUSION: An alert-based CDS strategy increased anticoagulation in high-risk hospitalized AF patients and reduced major adverse cardiovascular events, including MI and stroke. CLINICALTRIALS.GOV IDENTIFIER: NCT02339493.

Anticoagulation and Mortality Rates among Hospitalized Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is associated with an increased rate of mortality, heart failure, and stroke. We conducted an observational study to assess the relationship between anticoagulation and adverse clinical outcomes in hospitalized patients with AF. We performed a 5,000-consecutive-patient retrospective cohort analysis of anticoagulation prescription and 90-day outcomes in patients with AF hospitalized at Brigham and Women's Hospital from May 2008 to September 2014. All-cause mortality at 90 days was 5.4%. The frequency of death between hospital discharge and day 90 was lower in patients who were anticoagulated at discharge (2.8 vs. 7.1%, p < 0.001). Anticoagulation prescription at discharge was associated with a 60% reduction in death between discharge and day 90, after adjustment for confounding factors. Major adverse events at day 90, including death, myocardial infarction, stroke, and major bleeding, were more frequent in patients who were not prescribed anticoagulation at discharge (16.5 vs. 10.4%, p < 0.001). In multivariable regression analysis, prescription of anticoagulation at discharge predicted a lower mortality (adjusted odds ratio (OR), 0.4; 95% confidence interval (CI), 0.3-0.53) and lower major adverse event rate (adjusted OR, 0.64; 95% CI, 0.54-0.76) by day 90. In conclusion, all-cause mortality at 90 days was high among inpatients with AF. Patients with AF who were not prescribed anticoagulation at discharge had an increased risk of death at 90 days. Hospitalization represents a special opportunity to optimize cardiovascular risk reduction strategies, including anticoagulation.

Evaluation of the Effects of Quetiapine on QTc Prolongation in Critically Ill Patients.

Quetiapine, an atypical antipsychotic used in the intensive care unit (ICU) to manage delirium, has a possible adverse effect of corrected QT (QTc) interval prolongation. The objective of this analysis was to describe the impact of quetiapine on QTc interval prolongation in critically ill patients. This was a single-center, prospective cohort analysis of ICU patients who received quetiapine between October 2015 and February 2016. The major end point was the incidence of QTc prolongation greater than 60 milliseconds above baseline during therapy. Minor end points included median change in QTc interval and incidence of Torsades de Pointes (TdP). Univariate and multivariable analyses were performed to determine variables associated with higher risk of QTc prolongation. During the study period, 103 patients were enrolled in the analysis. QTc interval prolongation greater than 60 milliseconds occurred in 14 (13.6%) patients. The median change in QTc interval was 20 milliseconds. There were no cases of TdP. On multivariable analysis, the only variable associated with higher incidence of QTc prolongation was administration of a concomitant medication known to prolong the QTc interval ( P = .046). QTc prolongation was relatively uncommon among critically ill patients utilizing quetiapine. Patients receiving concomitant medications known to prolong the QTc interval may be at an increased risk.

Stability of Dexmedetomidine in 0.9% Sodium Chloride in Two Types of Intravenous Infusion Bags.

Dexmedetomidine is a frequently used sedative in the critical care setting. It is commercially available as a 4-mg/mL premixed compound or as 200-mcg/2-mL vials that must be further diluted prior to administration. However, limited data exist regarding the stability of dexmedetomidine admixtures compounded from the 200-mcg/2-mL vials, particularly for durations greater than 48 hours. Therefore, we performed stability testing on compounded dexmedetomidine prepared in two types of intravenous infusion bags for 14 days. Dexmedetomidine is available as 200-mcg/2-mL vials for dilution, 80-mcg/20-mL single-dose vials, and as 200-mcg/50-mL and 400-mcg/100-mL glass bottles. The stability of dexmedetomidine admixtures has previously been tested for 48 hours. The purpose of this analysis was to test the stability of dexmedetomidine admixtures for 14 days. Six dexmedetomidine admixtures of 200 mcg/50 mL were compounded in polyvinyl chloride and non-polyvinyl chloride bags, three of which were stored under refrigeration and three of which were kept at room temperature. High-performance liquid chromatography testing was performed to determine the concentration at Days 1 through 14. Stability was determined by taking the mean concentration of samples taken from each bag. All samples were tested in duplicate. A sample was considered stable if the concentration was greater than 90% of the original concentration. All samples retained over 90% of the drug under their respective storage conditions for the duration of the study. At time 0, the concentration of dexmedetomidine was between 3.99 mcg/mL and 4.01 mcg/mL. On Day 14, the mean concentration was between 95.8% and 98.9%, depending on the bag type and storage condition. The pH remained between 4.7 and 5.8 during the study period as has previously been reported in the literature. Dexmedetomidine admixtures of 200 mcg/50 mL were stable in both polyvinyl chloride bags and non-polyvinyl chloride bags for 14 days under refrigeration and 48 hours at room temperature. This represents the longest time allowable under United States Pharmacopeia Chapter <797> without the need for sterility testing.

Prospective evaluation of a bivalirudin to warfarin transition nomogram.

Bivalirudin may cause a falsely prolonged international normalized ratio (INR) that complicates the discontinuation of bivalirudin when used as a bridge to warfarin. To prospectively validate our novel bivalirudin to warfarin transition nomogram, adult patients who received bivalirudin as a bridge to warfarin between July 2015 and June 2016 were prospectively evaluated, utilizing our predictive nomogram. The major outcome of our analysis was the correlation between the predicted change in INR upon bivalirudin discontinuation based on the nomogram, and the actual change in INR upon bivalirudin discontinuation. The major outcome was analyzed using the Pearson's correlation test. A Pearson's correlation coefficient >0.6 was considered to be a strong correlation. Bivalirudin was used as a bridge to warfarin in 29 patients. The majority of patients (86%) included in the analysis had a ventricular assist device. The median initial bivalirudin rate was 0.07 mg/kg/h and the mean increase in INR when starting bivalirudin was 0.6. The mean final weight-based bivalirudin rate was 0.08 mg/kg/h and the mean change in INR after stopping bivalirudin was 0.7. The Pearson correlation coefficient between the predicted change in INR upon bivalirudin discontinuation and the actual change in INR upon bivalirudin discontinuation was 0.86 (p < 0.001). After bivalirudin discontinuation, 68% of patients had a therapeutic INR. The results of this prospective analysis successfully validated our novel bivalirudin to warfarin transition nomogram. There was a very strong correlation between the predicted change and actual change in INR upon bivalirudin discontinuation.

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

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.

Etanercept for the Treatment of Transplantation-Related Lung Injury After Hematopoietic Stem Cell Transplantation.

Although some data suggest favorable outcomes with use of etanercept for treatment of transplantation-related lung injury, concerns, such as development of new infections, still exist. The objective of this study was to describe the usage of etanercept at our institution and to evaluate the efficacy and safety of etanercept for this indication. Adult patients receiving at least one dose of etanercept for the treatment of pulmonary complications in patients after hematopoietic stem cell transplant from January 2005 to December 2010 were retrospectively evaluated. Outcomes included hospital mortality, incidence of new infection after etanercept administration, and time from administration of first dose of etanercept to infection. Seventeen patients who received etanercept at our institution from January 2005 to December 2010 were included. Four patients (24%) survived their hospital stay, and 3 patients (18%) were alive at both 100 days and 1 year from the initiation of etanercept therapy. Four patients (24%) developed at least one confirmed new infection after the initiation of etanercept therapy. Both moderate and long-term survival in our cohort was low. Caution and careful assessment of the risks and benefits of therapy should be taken before initiation of etanercept for transplantation-related lung injury.