Clinical paperElevated risk of venous thromboembolism in patients undergoing therapeutic hypothermia after cardiac arrest
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.
References (24)
- et al.
Thrombolysis during out-of-hospital cardiac arrest: a lesson in the law of diminishing returns
Crit Care
(2010) - et al.
Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism
N Engl J Med
(2004) - et al.
Evidence of platelet activation at medically used hypothermia and mechanistic data indicating ADP as a key mediator and therapeutic target
Arterioscler Thromb Vasc Biol
(2011) - et al.
Survival in the elderly after out-of-hospital cardiac arrest
Crit Care Med
(1993) - et al.
Does age affect outcomes of out-of-hospital cardiopulmonary resuscitation?
JAMA
(1990) - et al.
Survival from out-of-hospital cardiac arrest: effects of patient age and presence of 911 emergency medical services phone access
Am J Emerg Med
(1993) - et al.
Heart disease and stroke statistics-2020 update: a report from the American Heart Association
Circulation
(2020) - et al.
Heart disease and stroke statistics-2018 update: a report from the American Heart Association [published correction appears in Circulation. 2018 Mar 20;137(12):e493]
Circulation
(2018) - et al.
Improving neurological outcome after cardiac arrest: therapeutic hypothermia the best treatment
Anesth Essays Res
(2013) - et al.
Reversible inhibition of human platelet activation by hypothermia in vivo and in vitro
Thromb Haemost
(1994)et al.Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels
Circ Shock
(1990)