Evaluation of Bivalirudin's Effect on International Normalized Ratio to Determine an Appropriate Strategy for Transitioning to Warfarin.

Background: Direct thrombin inhibitors are recommended in confirmed or suspected heparin-induced thrombocytopenia. False elevation of the international normalized ratio (INR) occurs with these agents making bridging to warfarin challenging. There is limited data regarding bivalirudin's effect on INR. Objective: To evaluate bivalirudin's effect on the INR and determine a strategy for transitioning to warfarin. Methods: This was a retrospective observational study. Included patients were >18 years old receiving primary bridging therapy with overlapping bivalirudin and warfarin for at least 72 hours. Patients with administration of alternate anticoagulants during the transition interval or active major bleeding within 48 hours prior to bivalirudin initiation were excluded. The primary endpoint was to determine the effect on INR at first therapeutic activated partial thromboplastin time after bivalirudin initiation and prior to warfarin initiation. Secondary endpoints included change in INR 12 and 24 hours after bivalirudin initiation, change in INR 4 hours after bivalirudin cessation, and incidence of major bleeding or new thrombotic events. Results: Thirty-four patients met study criteria. For the primary endpoint, the change in INR at first therapeutic activated partial thromboplastin time was 0.37 (range = 0.28-0.48), which occurred at 8.4 hours (range = 4.6-14.2; n = 14). INR increased at 12 and 24 hours by a median of 0.55 and 0.5 from baseline, respectively. Median change in INR 4 to 8 hours post-bivalirudin cessation was -0.48. Conclusion: Targeting an INR > 2.5 when bridging to warfarin will account for this false elevation and maintain an INR above 2.0 on bivalirudin discontinuation.

In vitro efficacy of antibiotic beads in treating abdominal vascular graft infections.

OBJECTIVE: Abdominal aortic vascular graft infection often involves several different organisms. Antibiotic polymethyl methacrylate (PMMA) beads may be effective in controlling infection after débridement, but bacterial species identification and antibiotic susceptibility are often not available at the time of operation, generating a need for a broad-spectrum drug combination for empirical use. We sought to determine an effective antibiotic in PMMA beads for use in abdominal vascular graft infection. METHODS: PMMA beads were impregnated with combinations of antibiotics, consisting of daptomycin, tobramycin, and meropenem. Antibiotics were selected on the basis of activity spectrum and heat stability. Beads were placed on separate agar plates with vancomycin-resistant Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus epidermidis, and methicillin-resistant Staphylococcus aureus. Antibiotic inhibition was recorded by use of a modified agar-based disk-diffusion method. RESULTS: Daptomycin alone was not active against K. pneumoniae (average = 0 mm). Tobramycin alone was not active against vancomycin-resistant E. faecalis, K. pneumoniae, or methicillin-resistant S. aureus. Tobramycin and daptomycin in combination had moderate broad-spectrum activity with 8- to 14-mm mean inhibition halos. Meropenem showed strong activity against all tested organisms with >15-mm mean inhibition halos. The addition of daptomycin to meropenem provided improved coverage of gram-positive organisms. The presence of tobramycin reduced the efficacy of meropenem. CONCLUSIONS: Antibiotic PMMA beads containing 10% meropenem with 2.5% daptomycin had excellent in vitro activity against typical bacterial species associated with abdominal vascular graft infections. The addition of antibiotic beads may be a useful adjunct in managing such cases. Further studies are required to determine efficacy in clinical practice.

The impact of drug shortages on the pharmacy, nursing, and medical staff's ability to effectively care for critically ill patients.

Managing drug shortages has become a daily requirement for health care providers in the critical care environment. Drug shortages impact the practice of different disciplines in various ways, and the perceptions of the underlying causes and appropriate management of drug shortages vary among physicians, nurses, and pharmacists as well. Frequently, these differences can lead to tension between disciplines and feelings of frustration, anger, and helplessness. Understanding the reasons behind drug shortages, the role each discipline has in managing shortages, and establishment of an effective method of communication between disciplines is key to reducing the tension and frustration that can be associated with drug shortages.

Efficacy and safety of a furosemide continuous infusion following cardiac surgery.

OBJECTIVE: To review the literature regarding the efficacy and safety of continuous intravenous infusion of loop diuretics following cardiac surgery. DATA SOURCES: Articles were identified through a MEDLINE search (1966-March 2006) using the key words furosemide, bumetanide, torsemide, ethacrynic acid, loop diuretics, continuous infusions, intravenous infusions, surgery, cardiac surgery, cardiovascular surgery, and thoracic surgery. Search results were limited to studies in human subjects published in English. Additional references were identified through review of the bibliographies of the articles cited. STUDY SELECTION AND DATA EXTRACTION: All clinical trials and observational reports identified that evaluated or described the efficacy and/or safety of a continuous infusion of a loop diuretic in adult or pediatric patients who had undergone cardiac surgery were included in this review. DATA SYNTHESIS: Loop diuretics are often used to promote diuresis following cardiac surgery. Studies in patients who have undergone cardiac surgery have demonstrated that a more consistent and sustained diuresis is produced by a continuous infusion of furosemide compared with intermittent bolus doses of furosemide. However, there does not appear to be a significant difference in total urine output or change in serum electrolyte levels when furosemide is administered as a continuous infusion compared with intermittent bolus doses. CONCLUSIONS: A continuous infusion of furosemide is an effective and safe method of diuresis in patients undergoing cardiac surgery.

Continuous infusion versus intermittent bolus dosing of vecuronium in patients receiving therapeutic hypothermia after sudden cardiac arrest.

STUDY OBJECTIVE: To compare the effects of vecuronium administered as an intravenous continuous infusion versus intermittent bolus doses in patients treated with therapeutic hypothermia after sudden cardiac arrest (SCA). Design. Retrospective medical record review. SETTING: Cardiac care unit of a university-affiliated, level I trauma center. PATIENTS: Of 123 adults treated with therapeutic hypothermia after SCA, 80 received continuous-infusion vecuronium 0.8 µg/kg/minute started 2 hours after cooling began or if shivering occurred (January 1, 2004-December 31, 2007), and 43 received intermittent boluses of vecuronium 0.05 mg/kg every 2 hours (January 1, 2008-September 30, 2009). MEASUREMENTS AND MAIN RESULTS: The degree of neuromuscular blockade was measured with a train-of-four (TOF) test. Primary outcomes evaluated were time to achieve goal TOF response and percentage of time the TOF response was maintained at goal. Secondary outcomes included total daily dose of vecuronium, the vecuronium dose needed to achieve goal TOF response, percentage of TOF measurements above or below goal, and time to return of spontaneous respirations and time to extubation after the last dose of vecuronium. The goal TOF response was achieved significantly earlier in the bolus group than the continuous-infusion group (mean 5.9 vs 11.3 hrs, p=0.008). The mean total daily dose of vecuronium administered in the bolus group was significantly lower than that in the continuous-infusion group (51.7 vs 76.9 mg, p=0.002). The mean percentage of TOF measurements above goal was higher in the continuous-infusion group (33% vs 16%, p<0.0001), and the mean percentage of TOF measurements below goal was higher in the bolus group (43% vs 29%, p<0.0001). The median time to return of spontaneous respirations (6 vs 11 hrs, p=0.017) and time to extubation (29.5 vs 89.5 hrs, p<0.0001) were significantly shorter in the continuous-infusion group than the bolus group. CONCLUSION: Intermittent boluses of vecuronium were more effective in reaching a goal TOF response earlier compared with continuous-infusion vecuronium in patients treated with therapeutic hypothermia. The two dosing strategies were equally effective at maintaining a goal TOF response despite patients receiving a significantly lower daily dose of vecuronium in the intermittent-bolus group.