key: cord-0915910-4rxdrol8
authors: San Norberto, EM; De Haro, J; Peña, R; Riera, L; Fernández-Caballero, D; Sesma, A; Rodríguez-Cabeza, P; Ballesteros, M; Gómez-Jabalera, E; Taneva, GT; Aparicio, C; Moradillo, N; Soguero, I; Badrenas, AM; Lara, R; Torres, A; Sala, VA; Vaquero, C
title: OUTCOMES AFTER VASCULAR SURGERY PROCEDURES IN PATIENTS WITH COVID-19 INFECTION: A NATIONAL MULTICENTRE COHORT STUDY (COVID-VAS)
date: 2021-01-22
journal: Ann Vasc Surg
DOI: 10.1016/j.avsg.2021.01.054
sha: c096ef44d9e87a2eb00afa8e22ccd197ce9cb82b
doc_id: 915910
cord_uid: 4rxdrol8

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicentre, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary endpoint was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (p=0.009), American Society of Anesthesiologists (ASA) classification IV (p=0.004), preoperative lymphocyte count <0.6 (x10(9)/L) (p=0.001) and lactate dehydrogenase (LDH)>500 (UI/L) (p=0.004), need for invasive ventilation (p=0.043), postoperative acute renal failure (p=0.001), ARDS (p=0.003) and major amputation (p=0.009) as independent variables associated with mortality. Preoperative coma (p=0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (p=0.043), lymphocytes <0.6 (x10(9)/L) (p=0.019) leucocytes>11.5 (x10(9)/L) (p=0.007) and serum ferritin>1800 mg/dL (p=0.004), bilateral lung infiltrates on thorax computed tomography (p=0.025), and postoperative acute renal failure (p=0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (p=0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age>65 years, preoperative lymphocytes <0.6 (x10(9)/L) and LDH>500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.

The outbreak of coronavirus 2019 (COVID- 19) , an emerging infectious syndrome caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, constitutes the greatest public health emergency of this century. On January the 30th 2020, the World Health Organization announced that the COVID-19 epidemic was a public health emergency of international concern. COVID-19 has contributed to an enormous adverse impact globally. While the population continues to be affected by the whole spectrum of pre-existing diseases, hospitals were swamped with a massive number of COVID-19 patients, so in this context, the majority of surgical departments were forced to re-schedule their activity giving priority to urgent or emergent and non-deferrable cases. Our knowledge of COVID-19 is still rapidly evolving but, to date, we do not yet know the complete impact of this pandemic regarding vascular surgery. Patients with vascular diseases are especially prone to the development of complications if infected by The COVID-19 pandemic has significantly altered the practice of medicine, has In this article, we will focus on the detailed clinical outcomes when performing vascular surgery procedures for COVID-19 patients. The most important real-world registry is the CovidSurg Cohort Study (Outcomes of surgery in COVID-19 infection: international cohort study), 3 this international multicentre cohort study aims to assess the outcomes of any type of surgery (including obstetrics) in patients with COVID-19

infection. The primary aim of the present prospective multicentre study was to describe the treatment, outcome, and prognostic factors for patients with COVID-19 infection undergoing vascular surgery procedures. We analyzed data from a prospective database of patients treated in Spanish centers. Data entry was managed by physicians involved in direct patient care and were collected in a prospectively maintained database. Data was collected and stored online through a secure server running the SEACV web application. This secure server allows collaborators to enter and store data in a secure system. A designated collaborator at each participating site was provided with project server login details, allowing them to securely submit data on to the system. Only anonymized data were uploaded to the database. No patient-identifiable data were collected. Data collected pertained comorbidities, physiological state, treatment/operation, and outcome. The quick Sepsis Related Organ Failure Assessment (qSOFA) and the Severity Score for Community-Acquired Pneunomia (CURB-65) were calculated based on the individual data points entered.

The inclusion criteria were adults (age>18 years) undergoing any type of vascular surgery procedure in an operating theatre, this includes open surgery, endovascular surgery and hybrid procedures. COVID-19 infection was confirmed with laboratory tests either before or after surgery. Urgent and emergent surgeries were included. Urgent surgery was defined as the ones that could wait until the patient was medically stable, but should have generally been done within 2 days. However, emergent surgery was defined as the cases that had to be performed without delay, and the patient had no choice other than immediate surgery if permanent disability or death was to be avoided. Patients who met the inclusion criteria would be included regardless of surgical indication (aneurysm, limb or visceral ischemia, carotid stenosis, vascular trauma), anesthetic type (local, regional, general), procedure type, or surgical approach.

Demographic, risk factors, preoperative status (analytical and hemodynamic monitoring values), thoracic X-ray or thoracic computed tomography scan results, surgical characteristics, COVID-19 treatments (antibiotics, antivirals, chloroquine and related drugs, corticosteroids, intravenous immunoglobulins, interferon, interleukin-6 receptor antagonist), postoperative outcome (dialysis, support ventilation or mechanical ventilation), hospital stay and ICU admission and prognosis were obtained. Preoperative comorbidities included smoking, asthma, 4 cancer history, chronic renal failure (creatinine level >150 mmol/L), chronic obstructive pulmonary disease (COPD), chronic heart failure, dementia, diabetes mellitus (oral hypoglycaemic medications and/or insulin), hypertension (>140/90 mmHg; antihypertensive medication), ischaemic heart disease, peripheral arterial disease and stroke (ischaemic or haemorrhagic stroke).

Postoperative complications considered were acute renal failure (defined according to KDIGO clinical practice guidelines) 5 

The primary endpoint of this analysis was to determine 30-day mortality in patients with COVID-19 infection who underwent vascular surgery. 7-day mortality, 30-day reintervention, respiratory failure, ARDS and sepsis were also analyzed as secondary endpoints.

Normally distributed continuous variables are summarized with mean and standard deviation and compared using independent group t tests when the data were normally distributed; otherwise, the Mann-Whitney test was used. Continuous variables were tested for normality using the Shapiro-Wilk's test. Categorical variables were expressed as frequencies and percentages and compared by Pearson's chi-square or Fisher's exact test.

For the binary outcomes concerning mortality within 30 days of surgery, univariate and multivariate logistic regressions were used. In the multivariate models, patient characteristics, comorbidities, vascular disease diagnosis, COVID-19 treatments and postoperative complications were used as covariables. Univariate and multivariate logistic regression analyses were performed, and odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Two sided p values<0.05 were considered statistically significant throughout. All the analyses were performed with the SPSS statistical software package (version 20.0; IBM Corporation, Somers, NY, USA). Table 2 Postoperative outcomes 

The COVID-19 pandemic has overwhelmed healthcare systems across the world, and has also affected specialized practices such as vascular surgery. Since the Spanish government declared the state of alarm on March 14th 2020, we have instituted significant changes to our routine vascular surgical activities. The majority of centers experienced a reduction in or cessation of patient services and elective cases while continuing emergency surgery in accordance with the recommendations provided by the Spanish Ministry of Health, to preserve hospital resources such as intensive care unit beds. In the same way as in Portugal we have seen a significant decrease in the number of vascular urgent and emergent cases, which is probably due to the population confinement measures and to patients being afraid to go to medical centers. 9 The experience from Singapore published by Tan et al., 10 described 6 types of elective operations that would be carried out during the COVID-19 pandemic: limb salvage surgery (bypass or endovascular approach), aortic aneurysm surgery, vascular oncology surgery, major and minor amputations, creation and salvage of arteriovenous fistula. In our series, lower limb revascularization (54.7%) was the most common diagnosis for surgery, followed by vascular trauma (5.3%). Whenever possible, Spanish vascular surgeons have opted for an approach that shortened the length of stay: use of local or regional anesthesia, endovascular aneurysm repair and percutaneous approach.

The need for intensive care has been considered a "critical key" for vascular surgery patients. Therefore, endovascular favored over open repair whenever possible to shorten hospital and ICU stay could improve the treatment of our patients. Nevertheless, the endovascular approach could be possible in only eight patients (10.7%) and the local or regional anesthesia in forty-eight patients (64.0%). This fact could be explained because lower limb revascularization (54.7%), and specifically thromboembolectomy, was the most frequent surgical procedure and is related with the reported high incidence of cardiovascular complications associated with COVID-19 infection, including systemic arterial embolism. 11 Sena and Gallelli reported an incremented incidence of patients with severe critical limb ischaemia undergoing amputation surgery during the COVID-19 pandemia. 12 A study published in 2021 with 49 patients of the New York Metro area with acute arterial thromboembolism, reported 10% of primary amputation, 18% of limb loss and 46% of intrahospital mortality. 13 In our series, seventeen (22.7%) patients required some type of amputation during hospital stay. Several studies have reported associated coagulopathy disorders in COVID-19 patients. These reports have highlighted a co-existing hypercoagulable state in patients with COVID-19, which may be associated with higher limb ischaemia and mortality. 14, 15 Bellosta et al. 16 patients with no prior vascular history. 17 Wynants et al. 18 published a systematic review of prediction models for prognosis of COVID-19 infection. Prognostic models for patients with diagnosis of COVID-19 included age and lymphocyte count as mortality predictors. In our series age >65 years and preoperative lymphocyte count <0.6 (x10 9 /L) were found as major mortality factors. Zhou et al., 19 in their retrospective, multicentre cohort study including 191 patients found older age (odds ratio 1.10 per year increase) associated with inhospital death. Further, this investigation also suggested also suggested higher SOFA score and D-dimer elevation on admission as mortality risk factors. In our investigation qSOFA score >2 was associated with postoperative ARDS incidence (OR 5.64) but not with mortality. Very high levels of D-dimer (9434.37±16564.8ng/mL) were found in our series, but no relation with mortality, postoperative complications or reoperation was found. Nevertheless D-dimer has been described as a predictor of disease deterioration in several studies. 20 Other laboratory examinations such as leucopenia, leukocytosis, aspartate amino transferase, creatinine, hypersensitive cardiac troponin, ferritin, procalcitonine and LDH have been proposed as risk factors for complications and mortality. [21] [22] [23] Preoperative LDH>500 (UI/L) constituted in our report a significant predictor of 7-days (OR 1.92) and 30-days mortality (OR 9.75), meanwhile serum ferritin>1800 mg/dL (OR 2.00) was found as an independent risk factor for postoperative ARDS. This finding could reflect the inflammatory storm induced by the immune response against the COVID-19 infection.

The initial clinical sign for the detection of COVID-19 is pneumonia, however, other organ damages have been reported. 24, 25 In our study, postoperative acute renal injury has been significantly related with 7-days (p=0.001) and 30-days (p=0.001) mortality, ARDS (p=0.009) and respiratory failure (p=0.001). Pei et al, 24 There is no specific treatment for COVID-19, so treatment is symptomatic, and oxygen support represents the major treatment intervention for patients with severe infection. Management is based mainly on supportive therapy and on treating the symptoms and trying to prevent respiratory failure. High-flow oxygen has been usually used but some patients developed ARDS and warranted intubation with mechanical ventilation. The group of patients that required therapy with invasive ventilation was associated with a mortality almost 3 times higher at 7 and 30-days follow-up (OR 3.80, and OR 3.15, respectively). 

In conclusion, despite the very few patients undergoing vascular surgery procedures in Spain and Andorra during the COVID-19 pandemic, the short-term mortality has been significantly high. Clinical characteristics such as age>65 years and ASA classification grade IV, laboratory examinations such as preoperative lymphocyte count <0.6 (x10 9 /L) and LDH levels >500 (UI/L) and postoperative complications such as acute renal failure, ARDS and need for major amputation, have been described as independent negative survival risk factors. qSOFA score >2 was significantly associated with increased risk of postoperative ARDS and sepsis. 

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The authors thank Andaru Pharma for their technical support of the study database and investigator coordination.