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Heparin Dosing in Critically Ill Patients Undergoing Therapeutic Hypothermia Following Cardiac Arrest
Study Question: What are the effects of anticoagulation on intravenous unfractionated heparin (IVUH) in post-cardiac arrest therapeutic hypothermia (TH)?
Study Description: Study investigators conducted a two-center, retrospective analysis where the inclusion criteria were IVUH use for at least six hours and at least one aPTT during TH. Patients were followed by a pharmacy-driven heparin dosing service using an aPTT goal of 1.5-2 times baseline. Data were grouped based on temperature range: baseline/pre-hypothermia, TH, and post re-warming. All patients were monitored daily for major bleeding defined as: decrease of hemoglobin > 2 g/dL in 24 hours, transfusion(s) on 2 consecutive days, or major bleeding defined by an intensivist.
Results: Forty-six patients were included (47% in hospital arrest, 53% out of hospital arrest) with an average baseline aPTT of 34 ± 5 seconds prior to heparinization. The most common indications for IVUH were venous thromboembolism (n = 19, 41%) and acute coronary syndrome (n = 18, 39%). Thirty-four patients received IVUH for ≥ 24 hours, and 48% of patients received heparin boluses. During TH, the average aPTT was 142 ± 48 seconds, with an average initial aPTT of 153 ± 53 seconds. There was a significant increase between baseline aPTT vs. TH (p < 0.001) and TH vs. post-rewarming (p = 0.048) despite adjusting for multiple factors. Heparin dosing requirements were significantly lower during TH and only 7% of patients met target aPTT with initial dosing; the initial rate for these patients was 7 ± 1 unit/kg/hr (lower than protocol initial rate). An average rate of 5.7 ± 1 units/kg/hr was used in the 10 (22%) patients who met aPTT goals during TH. Three patients (7%) met criteria for major bleeding, and IVUH was subsequently discontinued. An additional 37 patients on prophylactic subcutaneous heparin were found to not have a statistically significant aPTT increase from baseline during TH.
Conclusion(s): TH alters the pharmacokinetics of IVUH.
Perspective: This is the largest study to investigate IVUH in TH. Two previous studies of IVUH in hypothermic conditions reported a decreased heparin half-life during hypothermia and increased aPTT – a findings consistent with this investigation. The authors of this study admit that heparin dosing protocols may have deviated from previous standard practice over time as participating centers became aware of increased aPTT during TH. This study also did not measure or report serum heparin levels, which might have helped identify the mechanism behind the increased aPTT during TH. Future research should focus on identifying this mechanism as well as evaluating proposed algorithms for TH IVUH dose adjustments.