1187: Impact of Targeted Temperature Management on Anti-Factor Xa Monitoring of Unfractionated Heparin

2020 ◽  
Vol 49 (1) ◽  
pp. 596-596
Author(s):  
Volodymyra Fedkiv ◽  
Song Oh ◽  
Angela Bingham ◽  
Justin Delic ◽  
Lauren Igneri ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Factor Xa ◽  
Targeted Temperature Management ◽  
Temperature Management

Evaluation of Unfractionated Heparin Dosing by Antifactor Xa During Targeted Temperature Management Post Cardiac Arrest

2021 ◽  
pp. 001857872110613
Author(s):  
Carrigan Belcher ◽  
Vivek Kataria ◽  
Klayton M Ryman ◽  
Xuan Wang ◽  
Joon Yong Moon ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Steady State ◽  
Unfractionated Heparin ◽  
Bleeding Event ◽  
Factor Xa ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Major Bleeding Event ◽  
Secondary Endpoints ◽  
Antifactor Xa

Purpose: To evaluate unfractionated heparin (UFH) dosing guided by antifactor Xa levels during targeted temperature management (TTM) post-cardiac arrest. Methods: Single-center, retrospective, observational study between January 1, 2014 and September 1, 2020. Patients initiated on TTM post-cardiac arrest and UFH were evaluated for inclusion. Patients included were ≥18 years of age and received weight-based UFH for ≥6 hours with 2 antifactor Xa levels drawn at target temperature. Excluded patients had no available temperature readings, received extracorporeal membrane oxygenation (ECMO) or factor Xa inhibitor (within 72 hours), or had hypertriglyceridemia or hyperbilirubinemia. The primary endpoint was to evaluate the proportion of patients that achieved a therapeutic antifactor Xa level between 0.3 and 0.7 IU/mL at steady state during TTM. Secondary endpoints included average UFH dose and average time to therapeutic antifactor Xa level at steady state; percent of first and total antifactor Xa levels subtherapeutic, therapeutic, and supratherapeutic during TTM. Results: A total of 73 patients met inclusion criteria. Of these, 21 patients achieved steady-state therapeutic antifactor Xa levels during TTM. The average time and dose to steady-state therapeutic antifactor Xa levels were 8.1 ± 4.5 hours and 9.9 ± 3.2 units/kg/hour. Overall, 61.7% of first and 47.4% of all antifactor Xa levels were supratherapeutic during TTM. Three (4.1%) patients experienced a major bleeding event. Conclusions: Guideline recommended UFH dosing, 12 or 18 units/kg/hour, during TTM resulted in more supratherapeutic antifactor Xa levels. Reduction of UFH infusion dose to 10 units/kg/hour may be required during TTM to maintain therapeutic antifactor Xa levels.

Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment

1993 ◽  
Vol 70 (06) ◽  
pp. 0909-0914 ◽  
Author(s):  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Dose Adaptation ◽  
Heparin Treatment ◽  
Lung Scan

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.

Comparison of the Non-Specific Binding of Unfractionated Heparin and Low Molecular Weight Heparin (Enoxaparin) to Plasma Proteins

1993 ◽  
Vol 70 (04) ◽  
pp. 625-630 ◽  
Author(s):  
Edward Young ◽  
Benilde Cosmi ◽  
Jeffrey Weitz ◽  
Jack Hirsh
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Plasma Proteins ◽  
Low Molecular Weight Heparin ◽  
Specific Binding ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
Fixed Amount

SummaryThe non-specific binding of anticoagulantly-active heparin to plasma proteins may influence its anticoagulant effect. We used low affinity heparin (LAH) essentially devoid of anti-factor Xa activity to investigate the extent and possible mechanism of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably because it displaces anticoagulantly-active heparin from plasma proteins. Although dextran sulfates of varying molecular weights also increased the anti-factor Xa activity, less sulfated heparin-like polysaccharides had no effect. These findings suggest that the ability to displace active heparin from plasma protein binding sites is related to charge and may be independent of molecular size. In contrast to its effect in plasma containing unfractionated heparin, there was little augmentation in anti-factor Xa activity when LAH was added to plasma containing low molecular weight heparin (LMWH), indicating that LMWH binds less to plasma proteins than unfractionated heparin. This concept is supported by studies comparing the anticoagulant activity of unfractionated heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and buffer, respectively. These findings may be clinically relevant because the recovered anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients with suspected venous thrombosis than in plasma from healthy volunteers. The reduced heparin recovery in patient plasma reflects increased heparin binding to plasma proteins because the addition of LAH augmented the anti-factor Xa activity. In contrast to unfractionated heparin, there was complete recovery of LMWH added to patient plasma and little increase of anti-factor Xa activity after the addition of LAH. These findings may explain why LMWH gives a more predictable dose response than unfractionated heparin.

Heart Rate and Neurological Outcomes in Patients Undergoing Targeted Temperature Management

2020 ◽  
pp. 088506662098250
Author(s):  
Chad M. Conner ◽  
William H. Perucki ◽  
Andre Gabriel ◽  
David M. O’Sullivan ◽  
Antonio B. Fernandez
Keyword(s):  
Heart Rate ◽  
Positive Association ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Neurological Outcomes ◽  
Neurologic Outcomes ◽  
Resuscitation Guidelines ◽  
The Mean ◽  
The Impact ◽  
The Relationship

Introduction: There is a paucity of data evaluating the impact of heart rate (HR) during Targeted Temperature Management (TTM) and neurologic outcomes. Current resuscitation guidelines do not specify a HR goal during TTM. We sought to determine the relationship between HR and neurologic outcomes in a single-center registry dataset. Methods: We retrospectively studied 432 consecutive patients who completed TTM (33°C) after cardiac arrest from 2008 to 2017. We evaluated the relationship between neurologic outcomes and HR during TTM. Pittsburgh Cerebral Performance Categories (CPC) at discharge were used to determine neurological recovery. Statistical analysis included chi square, Student’s t-test and Mann-Whitney U. A logistic regression model was created to evaluate the strength of contribution of selected variables on the outcome of interest. Results: Approximately 94,000 HR data points from 432 patients were retrospectively analyzed; the mean HR was 82.17 bpm over the duration of TTM. Favorable neurological outcomes were seen in 160 (37%) patients. The mean HR in the patients with a favorable outcome was lower than the mean HR of those with an unfavorable outcome (79.98 bpm vs 85.67 bpm p < 0.001). Patients with an average HR of 60-91 bpm were 2.4 times more likely to have a favorable neurological outcome compared to than HR’s < 60 or > 91 (odds ratio [OR] = 2.36, 95% confidence interval [CI] 1.61-3.46, p < 0.001). Specifically, mean HR’s in the 73-82 bpm range had the greatest rate of favorable outcomes (OR 3.56, 95% CI 1.95-6.50), p < 0.001. Administration of epinephrine, a history of diabetes mellitus and hypertension all were associated with worse neurological outcomes independent of HR. Conclusion: During TTM, mean HRs between 60-91 showed a positive association with favorable outcomes. It is unclear whether a specific HR should be targeted during TTM or if heart rates between 60-91 bpm might be a sign of less neurological damage.

Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

2021 ◽  
pp. 088506662110189
Author(s):  
Merry Huang ◽  
Aaron Shoskes ◽  
Migdady Ibrahim ◽  
Moein Amin ◽  
Leen Hasan ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Neurological Outcome ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Survival Outcomes ◽  
Pool Data ◽  
Good Neurological Outcome ◽  
Extracorporeal Cardiopulmonary Resuscitation ◽  
Over Time

Purpose: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. Methods: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data. Results: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR ( P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) ( P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. Conclusions: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

scholarly journals Echocardiographic parameters during prolonged targeted temperature Management in out-of-hospital Cardiac Arrest Survivors to predict neurological outcome – a post-hoc analysis of the TTH48 trial

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Thomas Hvid Jensen ◽  
Peter Juhl-Olsen ◽  
Bent Roni Ranghøj Nielsen ◽  
Johan Heiberg ◽  
Christophe Henri Valdemar Duez ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Neurological Outcome ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Left Ventricular Ejection ◽  
Secondary Outcome ◽  
Ventricular Ejection Fraction ◽  
Hospital Cardiac Arrest

Abstract Background Transthoracic echocardiographic (TTE) indices of myocardial function among survivors of out-of-hospital cardiac arrest (OHCA) have been related to neurological outcome; however, results are inconsistent. We hypothesized that changes in average peak systolic mitral annular velocity (s’) from 24 h (h) to 72 h following start of targeted temperature management (TTM) predict six-month neurological outcome in comatose OHCA survivors. Methods We investigated the association between peak systolic velocity of the mitral plane (s’) and six-month neurological outcome in a population of 99 patients from a randomised controlled trial comparing TTM at 33 ± 1 °C for 24 h (h) (n = 47) vs. 48 h (n = 52) following OHCA (TTH48-trial). TTE was conducted at 24 h, 48 h, and 72 h after reaching target temperature. The primary outcome was 180 days neurological outcome assessed by Cerebral Performance Category score (CPC180) and the primary TTE outcome measure was s’. Secondary outcome measures were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), e’, E/e’ and tricuspid annular plane systolic excursion (TAPSE). Results Across all three scan time points s’ was not associated with neurological outcome (ORs: 24 h: 1.0 (95%CI: 0.7–1.4, p = 0.98), 48 h: 1.13 (95%CI: 0.9–1.4, p = 0.34), 72 h: 1.04 (95%CI: 0.8–1.4, p = 0.76)). LVEF, GLS, E/e’, and TAPSE recorded on serial TTEs following OHCA were neither associated with nor did they predict CPC180. Estimated median e’ at 48 h following TTM was 5.74 cm/s (95%CI: 5.27–6.22) in patients with good outcome (CPC180 1–2) vs. 4.95 cm/s (95%CI: 4.37–5.54) in patients with poor outcome (CPC180 3–5) (p = 0.04). Conclusions s’ assessed on serial TTEs in comatose survivors of OHCA treated with TTM was not associated with CPC180. Our findings suggest that serial TTEs in the early post-resuscitation phase during TTM do not aid the prognostication of neurological outcome following OHCA. Trial registration NCT02066753. Registered 14 February 2014 – Retrospectively registered,

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