Elsevier

Resuscitation

Volume 162, May 2021, Pages 251-256
Resuscitation

Clinical paper
Elevated risk of venous thromboembolism in patients undergoing therapeutic hypothermia after cardiac arrest

https://doi.org/10.1016/j.resuscitation.2021.03.013Get rights and content

Abstract

Introduction

Targeted Temperature Management (TTM) reduces mortality and improves neurological outcomes after cardiac arrest. Cardiac arrest is considered a pro-thrombotic state. Endovascular cooling catheters may increase the risk of thrombosis. Targeted Temperature Management, however, increases fibrinolysis. The net outcome of these opposing effects remains largely unexplored. Moreover, the exact rate of venous thromboembolism (VTE) is uncertain in these patients. We sought to determine the incidence and potential predictors of VTE in patients undergoing TTM.

Methods

Single center retrospective analysis. Participants were age ≥18 years old, admitted with out-of-hospital or in-hospital cardiac arrest, underwent TTM between January 1, 2007 and April 30, 2019 with endovascular cooling catheter. A total of 562 patients who underwent TTM (Study group) were compared to 562 patients treated for ARDS (control group). This control group was based on presumed similarities in factors affecting VTE: intensive care setting, immobility, length of stay and likely presence of central venous catheters.

Results

Patients who underwent TTM had a significantly higher rate of VTE (6.6% vs 2.3%, p = 0.006) and deep vein thrombosis (DVT) (4.6% vs 1.3%, p = 0.011) when compared to control group. In multivariate analysis age, gender, race and hospital length of stay were not associated with development of VTE in the study group.

Conclusion

Patients undergoing TTM after cardiac arrest have statistically higher incidence of VTE and DVT compared to patients with ARDS. This risk is independent of age, gender, race or length of stay.

Introduction

Cardiovascular disease is the leading global cause of death.1 According to the 2018 secular trends from American Heart Association, the death rates for sudden cardiac arrest have declined steadily from 138 to 98 per 100,000 person-years.2 Targeted Temperature Management (TTM) is an important tool for the treatment of post-anoxic coma after cardiopulmonary resuscitation that has been shown to reduce mortality and improved neurological outcomes.3

TTM is known to impact the coagulation cascade. Current evidence suggests that TTM may be associated with a higher risk of bleeding at temperatures ≤35 °C, as clotting enzymes operate more slowly and platelets function less effectively.4, 5, 6, 7 Conversely, cardiac arrest and resuscitation in the absence of TTM has been associated with accelerated coagulation and fibrin deposition.8, 9

This counterbalance between the hemostatic deficit associated with hypothermia and the pro-thrombotic state of cardiac arrest places patients undergoing TTM at risk for both bleeding and clotting. Additionally, the use of endovascular catheters for TTM potentially further increases the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) due to both local and systemic effects of hypothermia on coagulation profiles.10, 11, 12

Deep vein thrombosis with and without pulmonary embolism seems to be an under-recognized clinical complication with a highly variable reported incidence of 2–67% depending on surveillance, modality of imaging and patient or catheter characteristics.9 Confirmation of the net clinical effects of these processes is integral to improving care for patients with out-of-hospital cardiac arrest receiving TTM.

Given the paucity and incongruity of current literature, we conducted a study to evaluate the incidence of DVT and PE in patients undergoing TTM and to identify associated risk factors, if any, with thrombosis. This may be useful in identifying high-risk patients and may help elucidate any potential benefit of routine DVT screening and/or prophylactic anticoagulation in patients undergoing TTM to prevent or treat DVT/PE.

Section snippets

Study design

This is a single-center retrospective case-control study. The study included two cohorts: one that underwent Targeted Temperature Management (TTM) and a control group that was treated for Acute Respiratory Distress Syndrome (ARDS) in medical Intensive Care Unit (ICU). The principal reasoning behind choosing this control group was similarities to the control group including ICU level of care, immobility, comparable length of stay and likely presence of central venous catheters.

Human subjects

Records of

Results

525 patients underwent TTM (study group) in the cardiac ICU and 562 were treated in the medical ICU with a diagnosis of ARDS (control group). Baseline characteristics of the study and control groups are shown in Table 1.

Patients undergoing TTM had a higher rate of VTE compared to controls (6.6% vs. 2.3% and; p = 0.006). The higher incidence of VTE was primarily attributable to a higher rate of DVT (4.6% vs. 1.3%; p = 0.011) as the rate of PE was not significantly different between study and

Discussion

In this single center, retrospective, case-control study we found that individuals in the TTM group were almost 2.9 times more likely to have a VTE than a person in the ARDS group.

Given the complex interplay of the hemostatic deficit and prothrombotic state associated with cardiac arrest, it is important to know the VTE risk for these patients. Because VTE has been associated with significantly higher morbidity,12, 13 mortality14, 15 and high economic burden.16 It is important for providers to

Limitations of the study

This is a retrospective study with data extracted from electronic medical records from more than a decade ago, the study relies on the accuracy of the charts with the assumption that a diagnosis was included the problem list by the provider. Some relevant factors that have potential to affect pathogenesis and incidence of VTE such as – time to ROSC, duration of hypoxemia and vasopressors could not be included in the study as these were not uniformly available for majority of the patients. For

Conclusion

Cardiac arrest patients undergoing therapeutic Targeted Temperature Management have a significantly higher rate of venous thromboembolism (VTE) compared with a control group of ARDS patients.

CRediT authorship contribution statement

Toishi Sharma: Conceptualization, Methodology, Data curation, Writing - original draft, Writing - review & editing. Jordan Kunkes: Conceptualization, Methodology, Editing. David O’Sullivan: Statistical support. Antonio Fernandez: Methodology, Supervision, Reviewing, Validation, Editing.

Funding

None.

Conflicts of interest

None.

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  • Cited by (0)

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