Highlights
- •SARS-CoV-2 infected patients have less use of acute revascularization treatments.
- •SARS-CoV-2 infected patients have higher odds of death or non-routine discharge.
- •No modifying effect of acute revascularization treatments on outcomes.
Abstract
Objectives
Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus maybe candidates for acute revascularization treatments (intravenous thrombolysis and/or mechanical thrombectomy).
Materials and Methods
We analyzed the data from 62 healthcare facilities to determine the odds of receiving acute revascularization treatments in severe acute respiratory syndrome coronavirus infected patients and determined the odds of composite of death and non-routine discharge with severe acute respiratory syndrome coronavirus infected and non-infected patients undergoing acute revascularization treatments after adjusting for potential confounders.
Results
Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments (odds ratio 0.6, 95% confidence interval 0.5–0.8, p = 0.0001). Among ischemic stroke patients who received acute revascularization treatments, severe acute respiratory syndrome coronavirus infection was associated with increased odds of death or non-routine discharge (odds ratio 3.0, 95% confidence interval 1.8–5.1). The higher odds death or non-routine discharge (odds ratio 2.1, 95% confidence interval 1.9–2.3) with severe acute respiratory syndrome coronavirus infection were observed in all ischemic stroke patients without any modifying effect of acute revascularization treatments (interaction term for death (p = 0.9) or death or non-routine discharge (p = 0.2).
Conclusions
Patients with acute ischemic stroke with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments. Severe acute respiratory syndrome coronavirus infection was associated with a significantly higher rate of death or non-routine discharge among acute ischemic stroke patients receiving revascularization treatments.
Key Words
Introduction
Our understanding of outcomes in acute ischemic stroke patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following acute revascularization treatments (as intravenous thrombolysis and/or thrombectomy) is based on small case series.
1
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An international panel4
cautioned regarding the potential for high rate of death or disability and post thrombolytic intracerebral hemorrhage (ICH)s in acute ischemic stroke patients with SARS-CoV-2 infection due to elevated concentrations of inflammation and hypercoagulability markers such as leukocytosis, and C reactive protein and D dimers and multisystem dysfunction.4
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and recommended further studies to address these concerns.4
We performed this analysis to understand utilization and associated outcomes of acute revascularization treatments in acute ischemic stroke patients with SARS-CoV-2 infection.Methods
We analyzed the data from the Cerner de-identified COVID-19 dataset.
8
, C. Corporation. Cerner provides access to de-identified patient data for COVID-19 research and vaccine development. https://www.cerner.com/newsroom/cerner-provides-access-to-de-identified-patient-data-for-covid-19-research-and-vaccine-development. Published 2020. Accessed.
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which included data from 62 contributing Cerner Real-World Data health systems from United States between December 1, 2019 and January 1, 2021. The dataset is available through Cerner Corporation after submission and approval of research protocol and analysis plan. The dataset includes data for patients who qualified for inclusion based on the following criteria:- (1)Patient has a minimum of one emergency department or inpatient encounter with a discharge diagnosis code that could be associated with exposure to or clinical suspicion of SARS-CoV-2 infection; OR
- (2)Patient has a minimum of one emergency department or inpatient encounter with a positive laboratory test for a SARS-CoV-2 infection.
Our analysis included patients with prior medical history from the past 5 years to ensure completeness of the records of potential comorbidities which constituted approximately 76% of the total cohort. Patients in whom no previous medical encounter occurred during the past 5 years were excluded. Encounters with missing data for certain non-essential variables such as gender were included.
In general, the Cerner de-identified COVID-19 dataset comprise more than 100 clinical and nonclinical variables associated with hospital stays, including primary and secondary diagnoses, primary and secondary procedures, patients' admission and discharge status, and patient demographic information. Cerner Corporation has established Health Insurance Portability and Accountability Act-compliant operating policies to establish de-identification for Cerner Real-World Data.
We used the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) primary diagnosis codes I63, I65 and I66 to identify the patients admitted with acute ischemic stroke. We also used ICD-10 procedure codes to estimate the proportion of patients who underwent mechanical thrombectomy (03CG3ZZ, 03CG3Z7, 03CH3Z7, 03CJ0ZZ, 03CJ3ZZ, 03CK3Z7, 03CK3ZZ, 03CL3Z7, 03CL3ZZ, 03CL0ZZ, 03CP3ZZ, 03CY3ZZ, 00C73ZZ) and/or intravenous thrombolysis administration (3E03317 and 3E06317). The ICD-10-CM codes were also used to identify the patients with other medical co-morbidities and in-hospital events: hypertension (I10, O10.0, O10.9, I16 and I67.4), diabetes mellitus (E08, E09, E10, E11 and E13), atrial fibrillation (I48), hyperlipidemia (E78), malignancy (Z85), nicotine dependence (F17), subarachnoid hemorrhage (I60), ICH (I61 and I62.9), pulmonary embolism (I26), acute myocardial infarction (I21), transient cerebral ischemic attack (G45), congestive heart failure (I09.81, I11.0 and I50) and peripheral vascular disease (I71, I79.0, I73.9, Z95.8 and Z95.9), pneumonia (J12-J18), respiratory failure (J96), urinary tract infection (N30.0, N30.9, N34.1, N34.2 and N39.0), acute kidney injury (AKI) (N17), septic shock (A41 and R65.21), hepatic failure (K72), cardiac arrest (I46), systemic inflammatory response syndrome(SIRS) (R65.1), and deep venous thrombosis (I82).
The primary outcome was in-hospital death. The secondary outcome was a composite of death or non-routine discharge (discharge to destinations other than home, such as short-term hospitals or other facilities including intermediate care and skilled nursing homes).
Statistical analysis
We performed a logistic regression analysis including all ischemic stroke patients to identify the odds of receiving acute revascularization treatments in the presence of SARS-CoV-2 infection after adjusting for age (age strata), gender, race/ethnicity, hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, malignancy, nicotine dependence, previous ischemic stroke, previous subarachnoid hemorrhage, previous ICH, previous acute myocardial infarction, previous transient cerebral ischemic attack, congestive heart failure, peripheral vascular disease, deep venous thrombosis, or previous pulmonary embolism.
We performed four logistic regression analyses to determine the independent effect of SARS-CoV-2 infection on 1/. death and 2/. death or non-routine discharge. Analysis 1 and 2 included patients who underwent acute revascularization treatments and analysis 3 and 4 included all acute ischemic stroke patients. Potential confounders included age (age strata), gender, race/ethnicity, hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, malignancy, nicotine dependence, previous ischemic stroke, previous subarachnoid hemorrhage, previous ICH, previous acute myocardial infarction, previous transient cerebral ischemic attack, congestive heart failure, peripheral vascular disease, deep venous thrombosis, previous pulmonary embolism. We entered use of acute revascularization treatments as an interaction term in analysis 3 and 4. Any p-values less than 0.05 are considered significant. All the analyses were done using R (version 3.6.1).
Results
Overall cohort of ischemic stroke patients
The proportions of men, African American, and Hispanic, and patients with diabetes mellitus, previous subarachnoid hemorrhage, congestive heart failure and deep venous thrombosis were significantly higher among those with SARS-CoV-2 infection (see Table 1). The in-hospital mortality (21.4% versus 7.0%, p < 0.0001) and non-routine discharges (76.1% versus 60.4%, p < 0.0001) were higher among acute ischemic stroke patients with SARS-CoV-2 infection than in those without SARS-CoV-2 infection (see Table 1).
Table 1Characteristics and outcomes for ischemic stroke patients according to SARS-CoV-2 infection status.
| Items | Patients with new ischemic stroke | Ischemic stroke patients who received acute revascularization treatments | ||||
|---|---|---|---|---|---|---|
| SARS-CoV-2 infection-present | SARS-CoV-2 infection -absent | p-value | SARS-CoV-2 infection-present | SARS-CoV-2 infection -absent | p-value | |
| Total | 2122 | 22217 | 96 | 1588 | ||
| Age (in years) | 69.8 ± 13.5 | 70.5 ± 13.7 | 0.8693 | |||
| < 35 | 38(1.8%) | 401(1.8%) | 0.9626 | 2(2.1%) | 38(2.4%) | 0.8466 |
| 35–49 | 124(5.8%) | 1218(5.5%) | 0.4861 | 10(10.4%) | 131(8.2%) | 0.4566 |
| 50–65 | 553(26.1%) | 5588(25.2%) | 0.3573 | 25(26%) | 441(27.8%) | 0.7131 |
| > 65 | 1407(66.3%) | 15010(67.6%) | 0.2383 | 59(61.5%) | 978(61.6%) | 0.9799 |
| Gender* | ||||||
| Men | 1167(55%) | 11183(50.3%) | 0.0004 | 63(65.6%) | 799(50.3%) | 0.0036 |
| Women | 947(44.6%) | 10953(49.3%) | 0.0004 | 33(34.4%) | 783(49.3%) | 0.0045 |
| Race/ethnicity | ||||||
| White, Non-Hispanic | 924(43.5%) | 13488(60.7%) | < 0.0001 | 47(49.0%) | 1000(63.0%) | 0.0060 |
| African American | 462(21.8%) | 3537(15.9%) | < 0.0001 | 10(10.4%) | 187(11.8%) | 0.6874 |
| Asian or Pacific Islander | 34(1.6%) | 454(2%) | 0.1659 | 1(1.0%) | 29(1.8%) | 0.5725 |
| Hispanic | 510(24%) | 3280(14.8%) | < 0.0001 | 26(27.1%) | 266(16.8%) | 0.0094 |
| Other | 192(9%) | 1458(6.6%) | < 0.0001 | 12(12.5%) | 106(6.7%) | 0.0299 |
| Pre-existing medical conditions | ||||||
| Hypertension | 1884(88.8%) | 19837(89.3%) | 0.4746 | 78(81.3%) | 1405(88.5%) | 0.0340 |
| Diabetes mellitus | 1315(62%) | 11085(49.9%) | < 0.0001 | 49(51%) | 676(42.6%) | 0.1035 |
| Atrial fibrillation | 735(34.6%) | 7380(33.2%) | 0.1852 | 34(35.4%) | 497(31.3%) | 0.3989 |
| Hyperlipidemia | 1680(79.2%) | 17270(77.7%) | 0.1276 | 72(75%) | 1211(76.3%) | 0.7785 |
| Malignancy | 351(16.5%) | 4355(19.6%) | 0.0006 | 12(12.5%) | 257(16.2%) | 0.3387 |
| Nicotine dependence | 443(20.9%) | 5896(26.5%) | < 0.0001 | 21(21.9%) | 437(27.5%) | 0.2275 |
| Previous ischemic stroke | 837(39.4%) | 8954(40.3%) | 0.441 | 23(24%) | 640(40.3%) | 0.0015 |
| Previous subarachnoid hemorrhage | 47(2.2%) | 296(1.3%) | 0.001 | 1(1%) | 10(0.6%) | 0.6266 |
| Previous intracerebral hemorrhage | 43(2%) | 419(1.9%) | 0.6506 | 2(2.1%) | 23(1.4%) | 0.6174 |
| Previous pulmonary embolism | 54(2.5%) | 485(2.2%) | 0.2793 | 3(3.1%) | 24(1.5%) | 0.2216 |
| Previous acute myocardial infarction | 183(8.6%) | 1893(8.5%) | 0.8705 | 4(4.2%) | 106(6.7%) | 0.3341 |
| Previous transient cerebral ischemic attack | 143(6.7%) | 1981(8.9%) | 0.0007 | 6(6.3%) | 114(7.2%) | 0.7312 |
| Congestive heart failure | 818(38.5%) | 7666(34.5%) | 0.0002 | 34(35.4%) | 445(28%) | 0.1189 |
| Peripheral vascular disease | 709(33.4%) | 7532(33.9%) | 0.6485 | 18(18.8%) | 461(29%) | 0.0302 |
| New in-hospital events | ||||||
| Pneumonia | 1398(65.9%) | 5871(26.4%) | < 0.0001 | 48(50%) | 298(18.8%) | < 0.0001 |
| Respiratory failure | 1236(58.2%) | 6417(28.9%) | < 0.0001 | 53(55.2%) | 432(27.2%) | < 0.0001 |
| Urinary tract infection | 848(40%) | 7493(33.7%) | < 0.0001 | 29(30.2%) | 431(27.1%) | 0.5125 |
| Acute kidney injury | 1215(57.3%) | 8793(39.6%) | < 0.0001 | 46(47.9%) | 467(29.4%) | 0.0001 |
| Septic shock | 872(41.1%) | 4867(21.9%) | < 0.0001 | 27(28.1%) | 228(14.4%) | 0.0003 |
| Hepatic failure | 96(4.5%) | 573(2.6%) | < 0.0001 | 0(0%) | 21(1.3%) | 0.2569 |
| Subarachnoid hemorrhage | 56(2.6%) | 486(2.2%) | 0.1781 | 6(6.3%) | 73(4.6%) | 0.4570 |
| Intracerebral hemorrhage | 89(4.2%) | 943(4.2%) | 0.9124 | 10(10.4%) | 157(9.9%) | 0.8660 |
| Acute myocardial infarction | 279(13.1%) | 2202(9.9%) | < 0.0001 | 5(5.2%) | 98(6.2%) | 0.7022 |
| Transient ischemic attack | 107(5%) | 1530(6.9%) | < 0.0001 | 2(2.1%) | 93(5.9%) | 0.1197 |
| Cardiac arrest | 166(7.8%) | 842(3.8%) | < 0.0001 | 7(7.3%) | 51(3.2%) | 0.0333 |
| Pulmonary embolism | 126(5.9%) | 993(4.5%) | 0.002 | 4(4.2%) | 58(3.7%) | 0.7950 |
| Systemic inflammatory response syndrome | 76(3.6%) | 682(3.1%) | 0.1947 | 2(2.1%) | 36(2.3%) | 0.9063 |
| Deep venous thrombosis | 218(10.3%) | 1957(8.8%) | 0.0238 | 2(2.1%) | 115(7.2%) | 0.0536 |
| Treatments provided | ||||||
| Received thrombolysis or thrombectomy | 96(4.5%) | 1588(7.1%) | < 0.0001 | - | - | - |
| Received only thrombolysis | 55(2.6%) | 751(3.4%) | 0.0525 | - | - | - |
| Received only thrombectomy | 35(1.6%) | 729(3.8%) | < 0.0001 | - | - | - |
| Intubation/mechanical ventilation | 344(16.2%) | 1514(6.8%) | < 0.0001 | 23(24%) | 173(10.9%) | 0.0001 |
| Outcome | ||||||
| Non-routine discharge | 1615(76.1%) | 13412(60.4%) | < 0.0001 | 76(79.2%) | 895(56.4%) | < 0.0001 |
| Expired in hospital | 455(21.4%) | 1556(7%) | < 0.0001 | 21(21.9%) | 104(6.5%) | < 0.0001 |
Abbreviation used: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2
Information regarding gender was not available in a small number of records
Utilization of acute revascularization treatment
The proportions of patients who received acute revascularization treatments among acute ischemic stroke patients with SARS-CoV-2 infection were lower than those without SARS-CoV-2 infection (4.5% versus 7.1%, p < 0.0001). Among ischemic stroke patients, 55(2.6%) and 751 (3.4%) received intravenous thrombolysis only, 35 (1.6%) and 729 (3.8%) received mechanical thrombectomy only, and 6 (0.3%) and 108 (0.5%) received both, in patients with and without SARS-CoV-2 infection, respectively. Patients with SARS-CoV-2 infection were significantly less likely to receive acute revascularization treatments among patients with ischemic stroke (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.5-0.8, p = 0.0001). Other factors associated with receiving receive acute revascularization treatments were African American race (OR 0.6, 95% CI 0.6-0.8, p < 0.0001), diabetes mellitus (OR 0.7, 95% CI 0.7–0.8, p < 0.0001), malignancy (OR 0.8, 95% CI 0.7–1.0, p = 0.01), previous subarachnoid hemorrhage (OR 0.5, 95% CI 0.3–0.9, p = 0.02), congestive heart failure (OR 0.8, 95% CI 0.7–0.9, p = 0.002), and peripheral vascular disease (OR 0.8, 95% CI 0.7–0.9, p = 0.001).
Characteristics and outcomes of patients receiving acute revascularization treatment
Patients with SARS-CoV-2 infection who received acute revascularization treatments were more likely to have pneumonia, respiratory failure, AKI, septic shock, cardiac arrest, and require intubation/mechanical ventilation. The proportion of patients who died during hospitalization (21.9% versus 6.5%, p < 0.0001) and those with non-routine discharge (79.2% versus 56.4%, p < 0.0001) were significantly higher among patients with SARS-CoV-2 infection compared with those without SARS-CoV-2 infection (See Table 1). The proportion of patients who experienced subarachnoid hemorrhage (1% versus 0.6%) or ICH (2.1% versus 1.4%) were similar between patients with and without SARS-CoV-2 infection.
Among all ischemic stroke patients who received acute revascularization treatments, SARS-CoV-2 infection was associated with increased odds of death (OR 4.1, 95% CI 2.3-7.2) (see Table 2) and death or non-routine discharge (OR 3.0, 95% CI 1.8–5.1) (see Table 2) after adjusting for potential confounders.
Table 2Summary of the results of the multivariate models.
| Variables | Odds Ratio (95% Confidence Intervals) | |||
|---|---|---|---|---|
| Patients who underwent acute revascularization treatments | All ischemic stroke patients | |||
| Predictors of death | Predictors of death or non-routine discharge | Predictors of death | Predictors of death or non-routine discharge | |
| Age < 35 years | 1.0(1.0–1.0) | 1.0(1.0–1.0) | 1.0(1.0–1.0) | 1.0(1.0–1.0) |
| Age 35-49 years | 2.9(0.6–14.7) | 1.3(0.6–2.7) | 1.3(0.8–2.1) | 1.3(1.0–1.6) |
| Age 50-65 years | 1.4(0.3–6.7) | 1.4(0.7–2.8) | 1.3(0.9–2.0) | 1.6(1.3–2.0) |
| Age > 65 years | 2.2(0.5–10.5) | 2.0(1.0–4.0) | 1.6(1.0–2.3) | 2.4(1.9–2.9) |
| Men | 1.0(0.7–1.5) | 0.8(0.6–1.0) | 1.2(1.1–1.4) | 0.9(0.9–1.0) |
| White | 1.0(1.0–1.0) | 1.0(1.0–1.0) | 1.0(1.0–1.0) | 1.0(1.0–1.0) |
| African American | 0.9(0.5–1.6) | 1.1(0.8–1.5) | 1.1(1.0–1.3) | 0.9(0.8–1.0) |
| Asian or Pacific Islander | 0.8(0.2–3.7) | 1.3(0.6–3.0) | 1.2(0.9–1.7) | 0.8(0.7–1.0) |
| Hispanic | 1.2(0.7–2.0) | 1.3(0.9–1.7) | 1.1(1.0–1.3) | 0.9(0.8–0.9) |
| Other race/ethnicity | 1.0(0.5–2.1) | 0.8(0.5–1.1) | 1.2(1.0–1.4) | 0.8(0.7–0.9) |
| Hypertension | 0.8(0.5–1.4) | 1.5(1.1–2.1) | 0.7(0.6–0.8) | 1.2(1.1–1.3) |
| Diabetes mellitus | 1.0(0.7–1.6) | 1.1(0.9–1.4) | 1.2(1.1–1.4) | 1.4(1.3–1.4) |
| Atrial fibrillation | 1.4(0.9-2.1) | 1.6(1.3-2.0) | 1.7(1.5-1.8) | 1.5(1.4–1.6) |
| Hyperlipidemia | 0.4(0.3–0.6) | 0.8(0.6–1.0) | 0.6(0.6–0.7) | 0.8(0.8–0.9) |
| Malignancy | 1.5(0.9–2.4) | 1.5(1.1–2.0) | 1.1(0.9–1.2) | 1.1(1.0–1.2) |
| Nicotine dependence | 0.5(0.3–0.9) | 1.2(0.9–1.5) | 0.9(0.8–1.0) | 1.1(1.0–1.1) |
| Previous ischemic stroke | 0.7(0.5–1.1) | 0.6(0.5–0.8) | 0.7(0.7–0.8) | 0.7(0.7–0.8) |
| Previous subarachnoid hemorrhage | 0(0–9999) | 0.8(0.2–2.9) | 1.1(0.8-1.6) | 1.4(1.1–1.8) |
| Previous intracerebral hemorrhage | 1.0(0.1–8.1) | 1.3(0.5–3.2) | 1.4(1.0–1.9) | 1.4(1.1–1.8) |
| Previous acute myocardial infarction | 1.3(0.6–2.7) | 0.9(0.6–1.3) | 1.0(0.9–1.2) | 1.0(0.9–1.1) |
| Previous transient cerebral ischemic attack | 0.6(0.2–1.6) | 0.6(0.4–0.9) | 0.8(0.6–0.9) | 0.9(0.8–1.0) |
| Congestive heart failure | 2.0(1.3–3.0) | 1.9(1.5–2.4) | 1.6(1.5–1.8) | 1.5(1.4–1.6) |
| Peripheral vascular disease | 1.4(0.9–2.1) | 0.9(0.7–1.1) | 1.2(1.1-1.3) | 1.0(1.0–1.1) |
| Deep venous thrombosis | 1.8(1.0–3.4) | 1.9(1.2–3.1) | 1.3(1.2–1.5) | 1.6(1.5–1.8) |
| Previous pulmonary embolism | 0.7(0.2–2.7) | 2.0 (0.7–5.3) | 1.0(0.7–1.3) | 1.0(0.8–1.2) |
| SARS-CoV-2 infection | 4.1(2.3–7.2) | 3.0 (1.8–5.1) | 3.4(3.0–3.9) | 2.1(1.9–2.3) |
| Received acute revascularization treatments | - | - | 1.0(0.8–1.2) | 0.9(0.8–1.0) |
| Interaction between acute revascularization treatments and SARS-CoV-2 infection | - | - | 1.0(0.6–1.8) | 1.4(0.9–2.4) |
Abbreviation used: SARS-CoV-2: severe acute respiratory syndrome coronavirus-2
Outcomes of acute ischemic stroke patients and interaction between SARS-CoV-2 infection and acute revascularization treatment
SARS-CoV-2 infection was associated with increased odds of death (OR 3.4, 95% CI 3.0–3.9) (see Table 2) and death or non-routine discharge (OR 2.1, 95% CI 1.9–2.3) (see Table 2) after adjusting for potential confounders. Utilization of acute revascularization treatments was not associated with significantly higher odds of death (OR 1.0, 95% CI 0.8–1.2) (see Table 2) and death or non-routine discharge (OR 0.9, 95% CI 0.8–1.0) (see Table 2). The interaction term between SARS-CoV-2 infection and acute revascularization treatments was not significant for either death (p = 0.9) or death or non-routine discharge (p = 0.2) in the multivariate model.
Discussion
Utilization of acute revascularization treatments
Patients who have acute ischemic stroke with SARS-CoV-2 infection are significantly less likely to receive acute revascularization treatments even though SARS-CoV-2 infection is not considered a contraindication for such treatments.
4
,15
Current guidelines recommend prompt revascularization treatments during the current pandemic because of the high mortality rate and severe neurological disability in untreated patients.- Powers W.J.
- Rabinstein A.A.
- Ackerson T.
- Adeoye O.M.
- Bambakidis N.C.
- Becker K.
- Biller J.
- Brown M.
- Demaerschalk B.M.
- Hoh B.
- et al.
Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American heart association/American stroke association.
Stroke. 2019; 50: e344-e418
16
, 17
, - Turc G.
- Bhogal P.
- Fischer U.
- Khatri P.
- Lobotesis K.
- Mazighi M.
- Schellinger P.D.
- Toni D.
- de Vries J.
- White P.
- et al.
European stroke organisation (ESO) - European society for minimally invasive neurological therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischaemic strokeendorsed by stroke alliance for Europe (SAFE).
Eur Stroke J. 2019; 4: 6-12
18
Several studies have reported a reduction in rates of utilization of acute revascularization treatments, and increase in time to treatment among acute ischemic stroke patients during the SARS-CoV-2 infection pandemic.19
, 20
, - Siegler J.E.
- Zha A.M.
- Czap A.L.
- Ortega-Gutierrez S.
- Farooqui M.
- Liebeskind D.S.
- Desai S.M.
- Hassan A.E.
- Starosciak A.K.
- Linfante I.
- et al.
Influence of the COVID-19 pandemic on treatment times for acute ischemic stroke: the society of vascular and interventional neurology multicenter collaboration.
Stroke. 2021; 52: 40-47
21
, 22
A relative reduction in number of mechanical thrombectomy procedures performed during the pandemic has been reported ranging from 21% in France, 25.3% in China, and 33% in in New York city compared with the procedures performed before the SARS-CoV-2 infection pandemic.16
,21
,23
An international study from 11 institutions from the United States and 7 international institutions found 8% reduction in mechanical thrombectomy procedures between 2019 and 2020, which was more prominent in regions with high prevalence of SARS-CoV-2 infection.22
Another study from 187 comprehensive stroke centers.24
reported a 12.7% decrease in mechanical thrombectomy procedures during SARS-CoV-2 infection pandemic with greater reduction in hospitals with higher SARS-CoV-2 infected patient admissions. Our findings suggest that the disproportionately lower utilization of acute revascularization treatments in SARS-CoV-2 infected patients may be contributing the overall decline observed in previous studies.The restricted use of acute revascularization treatments in SARS-CoV-2 infected patients may be due to increased delays from stroke onset to treatment consideration.
16
,21
,23
attributed to screening and preventive strategies to reduce transmission25
in initial evaluation, and performance of neuroimaging, and mechanical thrombectomy. There may be reluctance in using acute revascularization treatments due to presence of elevated concentration of inflammation and hypercoagulability markers4
,6
,7
and reports of high mortality in patients with SARS-CoV-2 infection who were treated with acute revascularization treatments.1
, 2
, 3
Patients with SARS-CoV-2 infection may be excluded due to hepatic dysfunction5
and coagulopathy (elevated prothrombin time, international normalized ratio, activated partial thromboplastin time, or reduced platelet count). The relatively high rate of renal insufficiency with subsequent AKI in patients with SARS-CoV-2 infection26
may delay or preclude administration of contrast for computed tomography angiography and/or perfusion to identify appropriate candidates.Outcomes of patients receiving acute revascularization treatments
Among patients who received acute revascularization treatments, patients with SARS-CoV-2 infection had significantly higher adjusted odds for in hospital death (OR 4.1) and also for death and non-routine discharge (OR 3.0). However, the higher rates for in hospital death and also for non-routine discharge were also seen in SARS-CoV-2 infected patients in overall cohort of acute ischemic stroke patients suggesting no unique effect of acute revascularization treatments. These adverse outcomes are related to higher rates of pneumonia, respiratory failure, AKI, septic shock, cardiac arrest, and requirement for intubation/mechanical ventilation in SARS-CoV-2 infected ischemic stroke patients. We did not see any modifying effect (interaction term p > 0.05) of acute revascularization treatments in the relationship between SARS-CoV-2 infection and in hospital death or composite endpoint of death and non-routine discharge. The proportions of patients with post-treatment ICH or subarachnoid hemorrhage were similar in patients with and without SARS-CoV-2 infection receiving acute revascularization treatments.
Implications for practice
Our results do not support withholding acute revascularization treatments in SARS-CoV-2 infected patients as we did not identify any higher risk of post treatment ICH or subarachnoid hemorrhage. However, the outcome of patients with SARS-CoV-2 infection and ischemic stroke is probably determined by the severity of multi-organ dysfunction and may obscure some or all of the benefit of acute revascularization treatments. An international panel
4
recommended assessment of the magnitude of organ dysfunction using Sequential Organ Failure Assessment score27
to delineate the overall care paradigm in acute stroke patients in accord with the expected prognosis. Other factors such as older age, cardiovascular diseases, secondary infections, acute respiratory distress syndrome, acute renal injury and laboratory findings of lymphopenia and elevated hepatic enzymes, and inflammatory markers associated with increased mortality may have to considered at time of decision making.- Moreno R.
- Vincent J.L.
- Matos R.
- Mendonca A.
- Cantraine F.
- Thijs L.
- Takala J.
- Sprung C.
- Antonelli M.
- Bruining H.
- et al.
The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. working group on sepsis related problems of the ESICM.
Intensive Care Med. 1999; 25: 686-696
28
, 29
, 30
Limitations
We used Cerner de-identified COVID-19 dataset
9
,14
which provides minimal details on the time interval between symptom onset to arrival, severity of neurological deficits, and diagnostic study results (neuroimaging and laboratory tests), or the exact reasons for exclusion from acute revascularization treatments. There is probably a selection bias towards inclusion of patients with greater severity of symptoms by limiting the analysis to emergency department and hospitalized patients. The dataset also depends on the accuracy of diagnosis and procedures codes. ICD-10 diagnosis codes have a high positive predictive value to identify acute ischemic stroke from the principle discharge diagnosis.31
The ICD-10 codes can identify 98% of all patients receiving intravenous thrombolysis and 87% of all patients receiving mechanical thrombectomy.32
The discharge functional outcome cannot be measured with the available data, and the closest index was using the destination of discharge as done in previous studies using Nationwide Inpatient Sample data.33
,34
Conclusions
Patients with acute ischemic stroke patients with SARS-CoV-2 infection were significantly less likely to receive acute revascularization treatments and had higher rates of death or non-routine discharge regardless of use of acute revascularization treatments.
Declaration of Competing Interest
AIQ has received consultation fees from AstraZeneca.
Grant support
WIB is supported by theNational Institutes of Health (5T32LM012410). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding source.
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Article info
Publication history
Published online: October 07, 2021
Accepted:
October 1,
2021
Received in revised form:
September 29,
2021
Received:
July 27,
2021
Footnotes
The work was performed in the neurology department of the University of Missouri.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106157
Copyright
© 2021 Elsevier Inc. All rights reserved.
