Evaluation of anticoagulation and nonsurgical major bleeding in recipients of continuous-flow left ventricular assist devices.

Continuous-flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7 days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24-h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow-up did not differ between groups and patients with major bleeding were not more likely to have a supra-therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.

Impact of time in therapeutic range after left ventricular assist device placement: a comparison between thrombus and thrombus-free periods.

The association between time in therapeutic range (TTR) and clinical outcomes in patients with left ventricular assist devices (LVADs) on chronic warfarin therapy is not well understood. This study assessed TTR using the Rosendaal Method prior to suspected or confirmed pump thrombosis or ischemic stroke. Each patient served as their own control. Characteristics and TTR in 1, 2, and 3 months prior to thrombus (thrombus period) were compared to a thrombus-free period during 6 months to 3 months prior to thrombus (control period). There were 30 thrombus events observed in 25 patients for a rate of 0.06 events per LVAD day. Average TTR (target INR = 2-3) over 3 months for patients combined in both the thrombus and control time period was 53.4%. TTR (target INR = 2-3) was 11.4% lower 1 month prior to thrombus than the comparable month in the control period (p = 0.029). The TTR (target INR = 1.8-2.5) was 11.8% lower in the thrombus time period compared to the control time period 2 months prior to thrombus (p = 0.032). Our study found an increased risk of thrombosis with lower TTR in months leading up to thrombus compared to a thrombus-free period.

Higher Maximum Doses and Infusion Rates Compared with Standard Unfractionated Heparin Therapy Are Associated with Adequate Anticoagulation without Increased Bleeding in Both Obese and Nonobese Patients with Cardiovascular Indications.

STUDY OBJECTIVE: To evaluate the time to achieve therapeutic activated partial thromboplastin time (aPTT) values and occurrence of bleeding based on standard unfractionated heparin (UFH) weight-based dosing recommendations compared with an aggressive weight-based UFH dosing strategy using higher maximum doses and infusion rates in both obese and nonobese patients who presented with non-ST-segment elevation myocardial infarction or unstable angina (NSTEMI/UA) or atrial fibrillation. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: A total of 197 adults were included who were admitted for NSTEMI/UA, atrial fibrillation, or other cardiac indications and received at least 6 hours of a continuous UFH infusion. Of those patients, 71 were treated with standard UFH dosing (60-unit/kg bolus [or maximum 4000 units] followed by an infusion of 12 units/kg/hour [or maximum 1000 units/hr]) between September 2013 and February 2014, and 126 patients received an aggressive UFH dosing strategy (60-unit/kg bolus [or maximum 10,000 units] followed by an infusion of 12 units/kg/hr [or maximum 2250 units/hr]) between October 2014 and March 2015. Patients in the standard dosing and aggressive strategy cohorts were further classified by body mass index status (normal, overweight, obese, and morbidly obese) and weight status. MEASUREMENTS AND MAIN RESULTS: A time-to-event analysis for achievement of therapeutic aPTT range (60-80 sec) was assessed. A significantly higher proportion of patients treated with the aggressive strategy achieved a therapeutic aPTT within 6 hours (23% vs 11%, p=0.043). The delay or failure to achieve therapeutic anticoagulation was particularly evident in obese patients in the standard dosing group. The mean ± SD initial infusion rate was 10.8 ± 1.4 units/kg/hour in the standard dosing group versus 12 ± 0.02 units/kg/hour in the aggressive strategy group (p=<0.0005). The occurrence of supratherapeutic aPTT values and the highest aPTT achieved were similar between the two dosing groups (p=0.817 and p=0.348, respectively). No bleeding events were reported in either group. CONCLUSION: Patients who had higher UFH maximum bolus doses and infusion rates achieved therapeutic anticoagulation more rapidly, without increased bleeding, and these doses can be adjusted for obese as well as nonobese patients. However, despite use of the higher doses, only 23% of patients achieved therapeutic aPTT values within 6 hours, suggesting that an even higher bolus dose and infusion rate may still be warranted.

Assessment of Bleeding and Thrombosis Based on Aspirin Responsiveness after Continuous-Flow Left Ventricular Assist Device Placement.

Pump thrombosis (PT) is a severe complication of left ventricular assist device (LVAD) support. This study evaluated PT and bleeding after LVAD placement in patients responsive to a standard aspirin dose of 81 mg using platelet inhibition monitoring compared with initial nonresponders who were then titrated upward to achieve therapeutic response. Patients ≥ 18 years of age with initial placement of HeartMate II LVAD at our institution and at least one VerifyNow Aspirin test performed during initial hospitalization were included. The primary endpoints were bleeding and PT compared between initial aspirin responders and nonresponders. Of 85 patients, 19 (22%) were nonresponsive to initial aspirin therapy. Responders and nonresponders showed similar survival (p = 0.082), freedom from suspected/confirmed PT (p = 0.941), confirmed PT (p = 0.273), bleeding (p = 0.401), and incidence rates in PT and bleeding. Among the initial responders (<500 vs. 500-549 aspirin reaction units), there were no significant differences in survival (p = 0.177), freedom from suspected/confirmed PT (p = 0.542), confirmed PT (p = 0.159), bleeding (p = 0.879), and incidence of PT and bleeding. Platelet function testing may detect resistance to standard aspirin regimens used in LVAD patients. Dose escalation in initially nonresponsive patients to achieve responsiveness may confer a similar PT risk to patients initially responsive to standard aspirin dosing without increased bleeding risk.

High-Dose Sedation and Analgesia During Extracorporeal Membrane Oxygenation: A Focus on the Adjunctive Use of Ketamine.

Use of ketamine in patients requiring extracorporeal membrane oxygenation (ECMO) has rarely been reported, and the optimal dosing strategy remains unclear. A patient admitted with hypoxic respiratory failure required ECMO in addition to continuous infusion of low-dose ketamine following titration of opioid and sedative medications to high doses. After initiation of ketamine, infusion rates of opioids and/or sedatives were maintained or decreased. Recorded Richmond Agitation-Sedation Scale (RASS) scores were -4 to -5 and documented pain scores were 0. No adverse effects were reported while receiving low-dose ketamine. This case illustrates that use of low-dose ketamine infusion may be a useful adjunctive agent in patients receiving ECMO and high-dose opioid and sedative medications.

Potentially inappropriate medication use is associated with clinical outcomes in critically ill elderly patients with neurological injury.

BACKGROUND: Limited data suggest that potentially inappropriate medications (PIMs) impact outcomes in critically ill elderly patients. No data are available on the association between PIM use as well as drug burden index (DBI), which is a measure of PIM use, and clinical outcomes in neurocritical care elderly patients. This study evaluates whether PIM use and a higher DBI are associated with poor clinical outcomes in neurocritical care elderly patients. METHODS: PIMs were retrospectively identified in critically ill elderly patients admitted to the neuroscience intensive care unit (NSICU) from March to July 2011. DBI was calculated based on PIM doses. Relationships with clinical outcomes were evaluated. RESULTS: PIMs were prescribed to a majority (81.3 %) of the 112 patients. Opioids were most commonly associated with a decrease in Richmond Agitation Sedation Scale (RASS) scores (56 % of PIM doses). Time to recovery was significantly longer in patients with a higher PIM burden (≤2 PIMs: 8 h, >2 PIMs: 29 h; p = 0.02). There was a significantly longer NSICU and hospital length of stay (9 vs 2; 15 vs 5 days; p < 0.0001) as well as a lower Glasgow Coma Scale score upon discharge (14 vs 15, p = 0.02) in patients with a higher DBI after 72 h of hospitalization. There was no difference in mortality. CONCLUSIONS: PIM use and higher DBI scores were associated with poor clinical outcomes and longer lengths of stay. Further studies are needed to determine the impact of PIMs and DBI on mortality in neurocritical care elderly patients.