Materials and Methods
We undertook a single-center, retrospective analysis of consecutive patients admitted to our ICU for critical care support caused by COVID-19 between March 19, 2020, and June 23, 2020. This study was undertaken following institutional board review and the requirement for informed consent requirement was waived.
Unselected patients with COVID-19 requiring ICU, with or without ECMO, were admitted to our tertiary center ICU via one of two possible pathways: the first group was admitted on the ECMO pathway as defined by the national ECMO guidelines, and the other patients were transferred from other hospitals due to local ICU capacity issues.
All patients had COVID-19 infection confirmed on reverse transcription-polymerase chain reaction testing prior to admission. Unless contraindicated (i.e., intracranial hemorrhage, n = 1), all patients received prophylactic low-molecular-weight heparin (LMWH) at admission and continued or escalated to a treatment dose LMWH as indicated (D-dimer level > 10 times the upper limit of normal [2,600 ng/mL] and a platelet count > 100 × 109/L). Treatment was switched to unfractionated heparin (UFH) if the creatinine clearance fell below 30 mL/min, aiming for a heparin anti-Xa concentration of 0.3–0.7 international units (IU)/mL. Standard practice is to give a bolus dose of UFH at cannulation, followed by heparin infusion if there is no evidence of intracranial bleeding on the CT head within 24 hours of ECMO. The target heparin anti-Xa concentration was 0.2–0.3 IU/mL for patients on ECMO if there was no evidence of thrombosis or 0.3–0.5 U/mL if there was confirmed or high clinical suspicion of thrombosis. The target anti-Xa level in patients on LMWH was 05–1.0 IU/mL, and if there is evidence of thrombosis despite these levels, dose of LMWH increase by at least 20% and maintain anti-Xa levels of 1.0–1.2 IU/mL.
Routine practice is to perform contrast-enhanced CT (CECT) in all patients with COVID-19 who are admitted to ICU in our hospital. Local standard operating protocols were followed to transfer patients to and from the CT scanner that was located in close proximity to ICU. The scans were performed on the day of admission or as soon as clinically feasible. Repeat scanning, to monitor progress and evaluate evolving clinical issues, was undertaken as clinically indicated. All CT examinations were performed on COVID-19 dedicated 128-slice, dual-source CT scanner (Definition FLASH; Siemens, Erlangen, Germany). The standard imaging protocol comprises an unenhanced CT of the head followed by CT angiogram of the thorax (following administration of 100 mL contrast agent [Visipaque 350; GE Healthcare AS, Nycoveien 1–2, NO-0401, Oslo, Norway]) to achieve adequate enhancement of the pulmonary arteries and the aorta) and, finally, portal venous phase acquisition of the abdomen and pelvis to assess the abdominal/pelvic viscera and vessels. All CT examinations were independently reviewed by two consultant cardiothoracic radiologists with disagreements resolved by consensus.
Clinical characteristics, laboratory data, and outcomes were collected using the Electronic Patient Record. Imaging data were collated from the picture archiving and communication system (IMPACS-5.2; Agfa HealthCare, Mortsel, Belgium). Full blood count, biochemical profile, high-sensitivity C-reactive protein (hs-CRP), and coagulation tests were performed daily, including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer levels (with and without age-adjustment). Only the data on ICU admission were used for analysis.
The primary endpoint was the detection of any venous or arterial thrombus or associated complication (deep vein thrombosis, pulmonary embolism, mesenteric ischemia, aortic or peripheral arterial thrombosis, or cerebral ischemic attack). We also recorded length of stay (LOS) and survival to hospital discharge.
Among patients with COVID-19, we compared patients with, and without, thrombotic complications for the occurrence of thrombotic complications, survival, and LOS. Continuous variables are presented as mean and SD and were compared using Mann-Whitney U test.
Categorical variables are presented as numbers and proportions and were compared using Pearson chi-square tests or Fisher exact tests. Univariate and multivariate logistic regression analysis controlling for age, gender, diabetes, body mass index, and ethnicity were used to compare differences between patients with and without thrombotic complications, and survivors and nonsurvivors, as appropriate. A two-sided p value of less than 0.05 was considered statistically significant. Statistical analyses were done using SPSS v.10.0 (IBM Corp., Armonk, NY).
Crit Care Med. 2021;49(5):804-815. © 2021 Lippincott Williams & Wilkins