Risk Factors and Outcomes Associated with Prolonged Subtherapeutic Anticoagulation with Bivalirudin: A Retrospective Cohort Study.

BACKGROUND: Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin-induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy. OBJECTIVES: The primary objective was to identify factors associated with failure to achieve early therapeutic anticoagulation (ETA) with bivalirudin, defined as achievement of two consecutive therapeutic activated partial thromboplastin times (aPTTs) within 24 hours. Secondary objectives included evaluating whether failure to achieve ETA was a risk factor for clinical outcomes of interest including thromboembolism, hemorrhage, and mortality. PATIENTS/METHODS: This was a retrospective cohort study. Patients between the ages of 18 and 89 years treated with bivalirudin for 24 hours or longer were identified and classified as either achieving or failing to achieve ETA. RESULTS: Nonadherence to the dosing protocol (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.07-2.71) and creatinine clearance (CrCl) of 60 ml/min or greater (OR 2.99, 95% CI 1.12-7.97) were significantly associated with failure to achieve ETA in univariate analyses. Conversely, increasing age (OR 0.98, 95% CI 0.97-0.99) was significantly associated with achievement of ETA. Failure to achieve ETA was associated with a 4-fold increase in the odds of thromboembolism. CONCLUSIONS: Younger age, normal renal function, and nonadherence to the dosing protocol when targeting therapeutic anticoagulation is associated with increased risk of failure to achieve ETA. This confers an elevated risk of thromboembolism when using bivalirudin for the management of HIT or other coagulation disorders.

Perioperative use of blood products is associated with risk of morbidity and mortality after surgery.

BACKGROUND: Administration of blood products may be associated with increased morbidity and perioperative mortality in surgical patients. METHODS: Patients aged 18 + who underwent gastrointestinal surgery at the Ohio State University Wexner Medical Center 9/10/2015-5/9/2018 were identified. Multivariable logistic regression models were used to evaluate impact of blood product use on survival and complications, as well as to identify factors associated with receipt of transfusions. RESULTS: Among 10,756 patients, 35,517 units of blood products were transfused. Preoperative nadir hemoglobin was associated with receipt of blood product transfusion (OR 0.55, 95% CI 0.53, 0.68). After adjusting for patient and procedural characteristics, patients undergoing transfusion of blood products had an increased risk of perioperative mortality (OR 7.80, 95% CI 6.02, 10.10). CONCLUSIONS: The use of blood products was associated with increased risk of complication and death. Patient blood management programs should be implemented to provide rational criteria and guidance for the transfusion of blood products.

Considerations for analgosedation and antithrombotic management during extracorporeal life support.

Despite the immense growth in extracorporeal life support (ECLS) technology and experience, opportunity remains to better characterize the pharmacotherapeutic considerations during ECLS. Analgosedation can be particularly challenging in the ECLS population due to in drug-circuit interactions that may lead to decreased systemic concentrations and pharmacodynamic effect. ECLS also requires the use of antithrombotic agents to mitigate the prothrombotic state created by the artificial surface in the ECLS circuit. There are a number of coagulation monitoring tests available. However, optimal monitoring and management in ECLS has not been established. Heparin continues to be the anticoagulant of choice for most ECLS centers, however, there is growing interest in the use of parenteral direct thrombin inhibitors (DTI) in this population. Advances in understanding pharmacotherapeutic management have not kept up with the technological advances in this population. More investigation is warranted to gain a greater understanding of the pharmacotherapeutic implications, facilitate standardized evidence-based practices, and improve patient centered outcomes.

Quality Improvement Intervention to Decrease Prolonged Mechanical Ventilation After Coronary Artery Bypass Surgery.

BACKGROUND: In 2010, the incidence of prolonged mechanical ventilation (> 24 hours) after isolated coronary artery bypass graft (CABG) surgery was 26.9% at the study site, The Ohio State University Wexner Medical Center, compared with the national like-hospital rate of 10.9%. OBJECTIVES: To use the principles of lean management to reduce the incidence of prolonged mechanical ventilation and to assess the sustainability of that reduction over time. METHODS: A multidisciplinary prolonged ventilation task force conducted a gap analysis leading to 3 interventions: (1) a standardized extubation protocol, (2) dry erase boards in patients' rooms to facilitate team communication, and (3) edits of the postoperative order set within the electronic health record. Outcomes of mechanical ventilation in CABG patients before and after the interventions are compared. RESULTS: All target outcomes changed significantly after the interventions, including a reduction in the median hours of initial mechanical ventilation (from 11.4 hours to 6.9 hours, P < .001). The percentage of patients reintubated did not increase (a decrease from 11.8% to 3.5% was not significant, P = .08). The rate of prolonged ventilation decreased from 29.4% to 8.6% (P = .004), and this reduction was sustained for 4 years after the interventions. CONCLUSIONS: Success factors included the multidisciplinary task force and continual protocol reeducation among front-line staff.

A Primer on Clinical Pathways.

Leaders in health-system pharmacy are challenged to maintain the highest quality pharmacy service at the lowest cost. Clinical pathways are evidence-based road maps that assist in reducing variations in clinical practice. Integration of clinical pathways within the electronic health record further helps to facilitate evidence-based practice. This article reviews the evolution of the clinical pathways, describes their clinical and economic impact, and identifies ways pharmacy directors can successfully implement these pathways into their institutions. Pharmacy directors can utilize their skills in this area or task clinical pharmacists to serve as members of the clinical pathway development team to further enhance patient-centered pharmacy services.

The impact of body mass index on patient survival after therapeutic hypothermia after resuscitation.

OBJECTIVES: Therapeutic hypothermia improves survival in patients after cardiac arrest, yet the impact of body mass index (BMI) on survival is lesser known. We hypothesized that nonobese patients would have greater survival post-therapeutic hypothermia than obese patients. METHODS: We retrospectively evaluated 164 patients who underwent therapeutic hypothermia after resuscitation for cardiac arrest from January 2012 to September 2014. Logistic regression analysis was used to assess for survival based upon BMI and comorbidities (odds ratio, 95% confidence interval). RESULTS: Forty-one percent of patients were obese. Obese patients presented less frequently with ventricular fibrillation (P=.046) but had similar rates of pulseless electrical activity (P=.479) and ventricular tachycardia (P=.262) to nonobese patients. In multivariable analysis, BMI less than 30 kg/m(2), hypertension, presence of pacemaker/implantable cardioverter-defibrillator, high glomerular filtration rate, and low neuron-specific enolase were all associated with increased survival post-therapeutic hypothermia, respectively: 0.36 (0.16-0.78), 0.28 (0.12-0.66), 0.23 (0.08-0.62), 0.25 (0.11-0.56), and 0.37 (0.14-0.96). Other comorbidities demonstrated no association with survival. CONCLUSIONS: Body mass index at least 30 kg/m(2) compared with BMI less than 30 kg/m(2) was a significant risk factor for mortality post-therapeutic hypothermia protocol. Absence of history of hypertension, lack of pacemaker/implantable cardioverter-defibrillator, high neuron-specific enolase, and renal disease had greater associations with death. Larger studies will be needed to validate these findings.

Clinically suspected heparin-induced thrombocytopenia during extracorporeal membrane oxygenation.

PURPOSE: Patients receiving extracorporeal membrane oxygenation (ECMO) are at risk for thrombocytopenia including heparin-induced thrombocytopenia (HIT). The purpose of this study was to determine the frequency of suspected HIT in patients receiving ECMO and unfractionated heparin (UFH). MATERIALS AND METHODS: We conducted a retrospective review in adult patients on ECMO. Patients were included if they received ECMO for at least 5 days and concomitant UFH. RESULTS: There were 119 patients who met inclusion criteria. Twenty-three patients (19%) had a heparin-platelet factor 4 immunoassay performed. Patients with suspected HIT had a significantly lower platelet count within the first 3 days of ECMO, 69×10(9)/L (22-126×10(9)/L) vs 87.5×10(9)/L (63-149×10(9)/L); P=.04. The lowest platelet count on the day of HIT testing was 43×10(9)/L (26-73), representing a 71% reduction from baseline. Twenty patients (87%) had an optical density score less than 0.4, and all patients had a score less than 1.0. A functional assay was performed in 7 patients (30%), with only 1 patient having laboratory-confirmed HIT. CONCLUSIONS: The evaluation of HIT occurred in a small percentage of patients, with HIT rarely being detected. Patients who had heparin-platelet factor 4 immunoassay testing exhibited lower platelet counts with a similar duration of ECMO and UFH exposure.

A review of inhaled nitric oxide and aerosolized epoprostenol in acute lung injury or acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are conditions associated with an estimated mortality of 40­50%. The use of inhaled vasodilators can help to improve oxygenation without hemodynamic effects. This article reviews relevant studies addressing the safety and efficacy of inhaled nitric oxide (iNO) and aerosolized epoprostenol (aEPO) in the treatment of life-threatening hypoxemia associated with ARDS and ALI. In addition, the article also provides a practicable guide to the clinical application of these therapies. Nine prospective randomized controlled trials were included for iNO reporting on changes in oxygenation or clinical outcomes. Seven reports of aEPO were examined for changes in oxygenation. Based on currently available data, the use of either iNO or aEPO is safe to use in patients with ALI or ARDS to transiently improve oxygenation. No differences have been observed in survival, ventilator-free days, or attenuation in disease severity. Further studies with consistent end points using standard delivery devices and standard modes of mechanical ventilation are needed to determine the overall benefit with iNO or aEPO.

Development and implementation of a nurse-driven, sliding-scale nomogram for bivalirudin in the management of heparin-induced thrombocytopenia.

PURPOSE: A simplified dosing nomogram to assist nurses in adjusting the rate of i.v. bivalirudin administration in cases of heparin-induced thrombocytopenia (HIT) is described. SUMMARY: To facilitate the availability of bivalirudin [corrected] as an alternative direct thrombin inhibitor (DTI) for patients with HIT at The Ohio State University Wexner Medical Center (OSUWMC), a team of clinical pharmacists developed a nomogram designed to simplify infusion dosage adjustments by nurses. In contrast to bivalirudin nomograms requiring patient-specific, percentage-based dose adjustments, the nomogram developed at OSUWMC specifies fixed adjustments (0.005 or 0.01 mg/kg/hr) according to the current activated partial thromboplastin time (aPTT) value relative to aPTT goals. During pilot testing over three years, the nomogram was used to guide dosage adjustments in 65 adult patients receiving continuous infusions of bivalirudin for suspected or confirmed HIT in intensive care units. Overall, the use of the nomogram resulted in adequate anticoagulation, with 53.7% of all measured aPTT values in the target range; 30.5% of aPTT values were below target, and 15.8% of values were above target. The median time to steady state was 11.0 hours (range, 5.0-31.8 hours), and bleeding rates were consistent with those reported in the literature. Nurse adherence to the nomogram was 100%, and no dosing errors occurred during a total of 487 dosage changes. Based on the pilot study results, the nomogram was refined to improve initial dosing for patients with creatinine clearance values of >30 mL/min; other refinements were made to enhance the safety of bivalirudin therapy for HIT in patients with severe renal impairment. CONCLUSION: A nurse-driven, sliding-scale nomogram for bivalirudin therapy in patients with HIT provided a simple dosing protocol and resulted in a high rate of adherence by nurses.

Prothrombin complex concentrate for warfarin-induced bleeding in a patient with a mechanical aortic valve.

Reversal of anticoagulation-induced bleeding in the perioperative period can be challenging, particularly with an unstable patient with a mechanical valve. We present a case of life-threatening bleeding successfully managed with a prothrombin complex concentrate as an alternative to fresh frozen plasma.

Direct thrombin inhibitors for management of heparin-induced thrombocytopenia in patients receiving renal replacement therapy: comparison of clinical outcomes.

PURPOSE: The clinical outcomes of patients receiving renal replacement therapy (RRT) and treated with direct thrombin inhibitors (DTIs) for the management of heparin-induced thrombocytopenia (HIT) were compared. METHODS: A retrospective evaluation of clinical outcomes of patients receiving RRT with a presumed diagnosis of HIT treated with lepirudin, argatroban, or bivalirudin was conducted. Inpatients at the University of Pittsburgh Medical Center from January 1, 1995, through March 1, 2008, were included if they were receiving either continuous or intermittent RRT and argatroban, bivalirudin, or lepirudin; were exposed to heparin within the preceding 100 days (including a heparin-treated pulmonary artery catheter) or had a documented heparin allergy; and had at least one of following: (1) an absolute platelet count of <150,000 cells/µL, (2) a decline in platelets of >50% from baseline before exposure to heparin, or (3) a documented diagnosis of thrombocytopenia. The primary outcome assessed was a triple composite endpoint of thrombosis, hemorrhage, and inhospital mortality. A secondary assessment compared the pharmacodynamic relationship between activated partial thromboplastin time and the triple composite. RESULTS: For the primary endpoint, there was no statistically significant difference observed among DTIs. In patients receiving RRT, a lack of a previous heparin allergy, the degree of International Normalized Ratio elevation, and lower serum albumin were significantly correlated with increased morbidity and the occurrence of the composite endpoint. CONCLUSION: No differences in adverse events or other clinical outcomes were observed in this retrospective evaluation of DTI use in patients receiving RRT with presumed HIT.

Calciphylaxis following coronary artery bypass surgery: an underappreciated cause of wound complications?

Wound complications following cardiac surgery are typically infectious and associated with a high morbidity and mortality. Calciphylaxis, vascular calcification of small and medium sized vessels, often associated with end-stage renal disease, can result in extensive tissue necrosis. We hypothesize that calciphylaxis is an under-recognized and under-reported precipitating wound and breast complication following coronary artery bypass surgery and thereby necessitates further study.

Extracorporeal membrane oxygenation for complex multiorgan system trauma.

With growing experience, the indications for salvage extracorporeal membrane oxygenation continue to expand. We describe a successful application of extracorporeal support in a polytrauma patient presenting with profound hypothermia, respiratory failure, and whom was later found to have an intracranial hemorrhage. We advocate the role of salvage therapy even in patients with complex pathophysiology despite perceived relative or absolute contraindications to extracorporeal support.

Shortness of breath: pulmonary embolism, ischemic heart failure, or both? The role of concomitant surgery.

We present a case of a patient who underwent successful concomitant surgical management of his massive pulmonary embolism and severe multivessel coronary disease. His presentation with shortness of breath prompted a comprehensive evaluation, which revealed both problems. This experience emphasizes the importance of considering both problems, because treating one but not the other could be catastrophic.

Nonconvective forces: a critical and often ignored component in the echocardiographic assessment of transvalvular pressure gradients.

Echocardiography is routinely used to assess ventricular and valvular function, particularly in patients with known or suspected cardiac disease and who have evidence of hemodynamic compromise. A cornerstone to the use of echocardiographic imaging is not only the qualitative assessment, but also the quantitative Doppler-derived velocity characteristics of intracardiac blood flow. While simplified equations, such as the modified Bernoulli equation, are used to estimate intracardiac pressure gradients based upon Doppler velocity data, these modified equations are based upon assumptions of the varying contributions of the different forces that contribute to blood flow. Unfortunately, the assumptions can result in significant miscalculations in determining a gradient if not completely understood or they are misapplied. We briefly summarize the principles of fluid dynamics that are used clinically with some of the inherent limitations of routine broad application of the simplified Bernoulli equation.

Temporary extracorporeal circulatory support and pulmonary embolectomy for catastrophic amniotic fluid embolism.

Amniotic fluid embolism is usually a life-threatening complication of an otherwise healthy pregnancy. Medical management of the coagulopathy and cardiovascular collapse is challenging and is often unsuccessful. We present a case and advocate the use of temporary circulatory support and pulmonary embolectomy in what would otherwise have been a fatal scenario.

Superior vena cava bypass with cryopreserved ascending aorta allograft.

Initially superior vena cava obstruction is typically managed by an endovascular approach. However, in some patients, particularly those in whom angioplasty and stenting is not technically possible, or those who have recurrent disease after previous endovascular repair, an open surgical approach may be indicated. Conduit choices for caval reconstruction are less than ideal; hence we describe a case using a cryopreserved aortic allograft.

Postvaccination Influenza 2009 H1N1 Respiratory Failure Requiring Extracorporeal Membrane Oxygenation.

The spread of pandemic Influenza A (H1N1-2009) was believed to have been attenuated by the effectiveness of worldwide vaccination initiatives. Despite the immunogenicity of a safe vaccine, we report a case of vaccine failure resulting in catastrophic influenza-associated respiratory failure.