Abstract
Introduction: Systemic inflammatory response syndrome (SIRS) is frequently observed following decannulation from extracorporeal membrane oxygenation (ECMO). Differentiating cytokine release due to infection from endothelial injury from cannula removal and/or discontinuation from the ECMO circuit has been shown to impact treatment and outcomes. This response, however, may be complicated in COVID-19 patients due to prevalent glucocorticoid and immune modulator use. It remains unclear whether COVID-19 infection and/or associated immune modulator use impact the incidence of SIRS following decannulation.
Objectives: The aim of this study is to investigate the incidence of the SIRS phenomenon and associated outcomes in patients with COVID-19 after ECMO decannulation.
Methods: An IRB-approved retrospective chart review of all patients who survived ECMO between June 31, 2010 and July 7, 2021 was done to identify patients who experienced SIRS within 48 hours of decannulation from ECMO support. Patients with COVID-19 were confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV2. SIRS was confirmed when two out of three of the following criteria were met: fever, leukocytosis, and/or initiation/escalation of vasopressors. Patients who developed post-ECMO SIRS were then distinguished based on the presence of infection. Infection was defined by the presence of either a new or positive culture following decannulation. We compared the incidence of SIRS and infection within 48 hours of decannulation in patients with and without COVID-19.
Results: We identified 227 eligible patients who survived ECMO. Twenty-eight patients (12%) had COVID-19. Of these patients, ten patients with COVID-19 (36%) experienced post-ECMO SIRS, including those with true SIRS (n=3) and associated infections (n=7). Five of the ten patients with COVID-19 who experienced post-ECMO SIRS were exposed to immune modulators within two weeks of decannulation. Ninety-five (42%) patients without COVID-19 developed post-ECMO SIRS. Thirty-day survival in COVID patients who experienced post-ECMO SIRS compared to COVID patients who did not experience post-ECMO SIRS was 73% vs. 94%. (p=0.11).
Conclusion: Post-ECMO SIRS is common. The incidence of SIRS following decannulation was similar when historically compared to non-COVID patients who survived ECMO in a previously reported cohort from our institution. Immune-modulation exposure within two weeks of decannulation did not affect the incidence of SIRS in patients with COVID-19.
Keywords: survival, infection, covid-19, sirs, ecmo
Introduction
Extracorporeal membrane oxygenation (ECMO) is a technology most often used to support patients with acute severe cardiac and/or respiratory failure and high mortality risk despite the use of maximal conventional therapy [1-3]. In the midst of a pandemic, ECMO was increasingly being used in patients worldwide with coronavirus disease 2019 (COVID-19) [4-6]. ECMO is intended to augment oxygenation and gas exchange with or without hemodynamic support to allow time for end-organ recovery. Patients are ultimately decannulated from ECMO once criteria for adequate tissue perfusion and organ recovery are met [6]. However, there are numerous complications that may occur after weaning from extracorporeal support, which may hinder subsequent recovery [6]. Development of systemic inflammatory response syndrome (SIRS) while on ECMO can occur due to a complex and multi-faceted innate inflammatory response to the foreign extracorporeal circuit [5-8]. Systemic inflammation can also occur due to the underlying disease process or secondary insults related to infection, prolonged ventilator support, aspiration, or extensive vascular injury [6-8]. SIRS has also been observed and, more recently, described in the literature following ECMO decannulation. Poorer outcomes are associated with those who have evidence of true infection and associated sepsis following decannulation [4]. It remains unclear whether COVID-19 or associated treatment with immune-modulating therapies affect the incidence of post-decannulation SIRS or infection. This retrospective chart review was conducted in order to identify and compare the incidence, risk factors, and associated outcomes of SIRS and infection following decannulation from ECMO in patients with and without COVID-19. This article was previously presented as a meeting abstract at the 2022 American Thoracic Society International Conference on May 15, 2022.
Materials and methods
We conducted an IRB-approved retrospective chart review of all patients who survived ECMO at Thomas Jefferson University Hospital between June 31, 2010 and July 7, 2021. Patients who died within 24 hours of ECMO cannulation were excluded. Patients who died within 48 hours of decannulation were also excluded since these deaths were presumably attributed to preceding organ failure or complications rather than the SIRS response. Patients with COVID-19 were confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV2. Per institutional protocol, all patients were confirmed to be afebrile without evidence of uncontrolled or active infection at the time of ECMO decannulation. ECMO decannulation was initially exclusively performed in the operating room with direct vessel repair; however, during COVID, bedside decannulation was increasingly performed to optimize resource utilization. All patients received perioperative antibiotics post-decannulation for 24 hours unless a predetermined course for controlled infection was being completed. SIRS was confirmed when two out of three of the following criteria (fever [>101.5 ℉], leukocytosis [white blood cell > 12,000 or 25% increase from prior baseline], and/or initiation/escalation of vasopressors) were met within 48 hours of decannulation. Conventional SIRS criteria, including tachycardia and tachypnea, were not used due to potential confounding effects related to concurrent analgesia and sedation, vasopressors, inotropes, neuromuscular blocking agents, deconditioning, or specific ventilator settings. Patients who developed post-ECMO SIRS were then distinguished based on the presence of infection. Infection was defined by either (a) a previously recognized infection during ECMO that was appropriately controlled at the time of decannulation or (b) new positive culture data from blood, sputum, urine, or stool assays following decannulation. Patients who developed SIRS criteria without infection were further characterized as having "true SIRS." Administration of immune modulating therapies, including tocilizumab, baricitinib, hydroxychloroquine, and glucocorticoids, during the treatment course for COVID-19 infection was also noted. Veno-arterial ECMO (VA-ECMO) via femoral cannulation was primarily used for patients with cardiogenic shock, whereas the majority of patients with respiratory failure underwent veno-venous ECMO (VV-ECMO) using either a single-site, dual-lumen right internal jugular (IJ) venous cannulation or traditional dual-site cannulation via the femoral and right IJ venous cannulations. A minority of patients with predominant respiratory failure received VA-ECMO due to concurrent heart failure, hypotension, or anatomical or technical limitations. ECMO circuits included a Rotaflow centrifugal pump (Maquet, Rastatt, Germany) and a Quadrox-D diffusion membrane hollow-fiber oxygenator (Maquet, Rastatt, Germany).
Statistical analysis
Data were expressed as a number paired with the percentage, mean, or median (quantile), as appropriate. The two groups were compared using chi-squared tests for categorical variables and standard t-tests for continuous variables. Statistical significance was accepted at a level of p = 0.05.
Results
We identified 227 eligible patients who survived ECMO. Twenty-eight patients (12%) had COVID-19. Of these, ten patients with COVID-19 experienced post-ECMO SIRS (36%), with a subset of five patients (50%) exposed to immune-modulating therapies within two weeks of decannulation. Among the ten with COVID-19 and SIRS, three had "true SIRS" (30%) and seven had SIRS associated with infection (70%).
Patients with COVID-19 who experienced post-ECMO SIRS had lower 30-day survival compared to patients with COVID-19 who did not experience post-ECMO SIRS (70% vs. 94%, p=0.09). Patients with COVID-19 who experienced post-ECMO SIRS were significantly older (54.6 vs. 46.2, p = 0.026); however, there were no other significant differences in other baseline demographics, pre-ECMO vital signs, pre-ECMO or pre-decannulation laboratory values, or listed complication rates (Table 1). There was no difference in ECMO duration (20.7 days vs. 19.5 days, p=0.87) when comparing COVID patients who developed SIRS and those who did not. Additionally, immune modulator exposure within two weeks of decannulation did not increase the risk of developing SIRS among patients with COVID-19 on ECMO (OR 0.89, 95% CI 0.186-4.224, p=0.883).
Table 1. Comparison of patients with COVID-19 with/without post-decannulation systemic inflammatory response syndrome.
ECMO: extracorporeal membrane oxygenation, VA: venoarterial; VV: veno-venous; FiO2: fraction of inspired oxygen; PEEP: positive end expiratory pressure; SIRS: systemic inflammatory response syndrome
| COVID+ with SIRS (n=10) | COVID+ without SIRS (n=17) | P-values | |
| Pre-ECMO demographics | |||
| Age (years) | 56.2 ± 8.0 | 46.2 ± 11.8 | 0.026 |
| Male | 7 (70%) | 12 (71%) | 0.974 |
| Body surface area (cm2) | 2.2 ± 0.2 | 2.0 ± 0.3 | 0.073 |
| Body mass index | 35.5 ± 8.0 | 34.0 ± 6.9 | 0.611 |
| ECMO strategy | |||
| VA | 0 (0%) | 0 (0%) | 1.000 |
| VV | 10 (100%) | 17 (100%) | 1.000 |
| Length on ECMO (days) | 20.7 ± 12.3 | 19.5 ± 20.4 | 0.868 |
| Comorbidities | |||
| Smoking | 1 (10%) | 2 (12%) | 0.888 |
| Coronary artery disease | 0 (0%) | 0 (0%) | 1.000 |
| Diabetes mellitus | 2 (20%) | 4 (24%) | 0.831 |
| Pre-ECMO vitals signs | |||
| Temperature (°F) | 99.9 ± 1.5 | 99.3 ± 1.6 | 0.345 |
| Heart Rate | 102.1 ± 28.2 | 107.5 ± 21.0 | 0.575 |
| Respiratory rate | 30.3 ± 5.9 | 27.4 ± 4.0 | 0.139 |
| Mean arterial pressure (mmHg) | 80.1 ± 17.1 | 85.6 ± 11.3 | 0.323 |
| FiO2 (%) | 93.0 ± 14.9 | 91.8 ± 12.4 | 0.823 |
| PEEP (cm) | 14.8 ± 3.6 | 15.1 ± 5.2 | 0.874 |
| Pre-ECMO laboratory data | |||
| White blood cell count (B/L) | 15.7 ± 8.2 | 15.0 ± 11.5 | 0.868 |
| Creatinine (mg/dl) | 1.0 ± 0.3 | 1.2 ± 1.5 | 0.683 |
| Bilirubin (mg/dl) | 0.7 ± 0.6 | 0.8 ± 1.0 | 0.777 |
| Aspartate aminotransferase (IU/L) | 58.2 ± 31.1 | 62.1 ± 30.0 | 0.750 |
| Alanine aminotransferase (IU/L) | 46.2 ± 30.2 | 65.3 ± 60.9 | 0.365 |
| Lactate (mmol/L) | 1.5 ± 0.7 | 1.7 ± 0.7 | 0.480 |
| Pre-decannulation laboratory data | |||
| White blood cell count (B/L) | 14.5 ± 6.4 | 13.6 ± 5.7 | 0.708 |
| Creatinine (mg/dl) | 1.1 ± 0.6 | 1.1 ± 1.1 | 0.999 |
| Bilirubin (mg/dl) | 0.6 ± 0.2 | 0.9 ± 0.9 | 0.312 |
| Aspartate aminotransferase (IU/L) | 60.1 ± 27.8 | 85.3 ± 118.0 | 0.516 |
| Alanine aminotransferase (IU/L) | 45.2 ± 28.2 | 80.1 ± 101.3 | 0.300 |
| Lactate (mmol/L) | 1.5 ± 0.3 | 1.4 ± 0.4 | 0.501 |
| Complications during ECMO | |||
| Acute kidney injury | 2 (20%) | 0 (0%) | 0.055 |
| Acute liver failure | 0 (0%) | 0 (0%) | 1.000 |
| Stroke | 0 (0%) | 0 (0%) | 1.000 |
| Intracranial hemorrhage | 0 (0%) | 1 (6%) | 0.434 |
| Cannulation site bleed | 1 (10%) | 1 (6%) | 0.693 |
| Gastrointestinal hemorrhage | 1 (10%) | 3 (18%) | 0.589 |
| SIRS phenomenon | |||
| Fever 24 hours post-decannulation | 9 (90%) | 5 (29%) | 0.002 |
| Leukocytosis 24 hours post-decannulation | 3 (30%) | 0 (0%) | 0.016 |
| Vasopressor use | 6 (60%) | 5 (29%) | 0.118 |
| Outcomes | |||
| 30-day survival | 7 (70%) | 16 (94%) | 0.088 |
When further analyzing the subgroup of COVID-19 patients who developed post-ECMO SIRS, there was no significant difference between patients who developed an infection and those who had true SIRS. The number of patients was insufficient to demonstrate a significant difference in 30-day survival when comparing true SIRS to infection-associated SIRS (66% vs. 75%, p=0.782) (Table 2).
Table 2. Subgroup analysis of COVID+ Patients who developed systemic inflammatory response syndrome response.
ECMO: extracorporeal membrane oxygenation, VA: venoarterial; VV: veno-venous; FiO2: fraction of inspired oxygen; PEEP: positive end expiratory pressure; SIRS: systemic inflammatory response syndrome
| True SIRS (n=3) | Infection (n=7) | P-value | |
| Pre-ECMO demographics | |||
| Age (years) | 55.7 ± 7.2 | 56.4 ± 8.8 | 0.907 |
| Male | 3 (100%) | 4 (57%) | 0.175 |
| Body surface area (cm2) | 2.1 ± 0.1 | 2.2 ± 0.3 | 0.599 |
| Body mass index | 33.3 ± 4.2 | 36.5 ± 9.3 | 0.692 |
| ECMO strategy | |||
| VA | 0 (0%) | 0 (0%) | 1.000 |
| VV | 3 (100%) | 7 (100%) | 1.000 |
| Length of ECMO (days) | 13.7 ± 6.0 | 23.7 ± 13.5 | 0.264 |
| Comorbidities | |||
| Smoking history | 1 (33%) | 0 (0%) | 0.107 |
| Coronary artery disease | 0 (0%) | 0 (0%) | 1.000 |
| Diabetes mellitus | 1 (33%) | 1 (14%) | 0.490 |
| Pre-ECMO vital signs | |||
| Temperature (°F) | 99.9 ± 1.7 | 99.9 ± 1.6 | 1.000 |
| Heart rate | 98.3 ± 44.8 | 103.7 ± 22.7 | 0.799 |
| Respiratory rate | 30.3 ± 4.5 | 30.3 ± 6.8 | 1.000 |
| Mean arterial pressure (mmHg) | 81.7 ± 8.1 | 79.4 ± 20.4 | 0.859 |
| FiO2 (%) | 90.0 ± 17.3 | 94.3 ± 15.1 | 0.701 |
| PEEP (cm) | 14.0 ± 5.3 | 15.1 ± 3.0 | 0.679 |
| Pre-ECMO laboratory data | |||
| White blood cell count (B/L) | 16.8 ± 10.7 | 15.2 ± 7.9 | 0.796 |
| Creatinine (mg/dl) | 0.9 ± 0.3 | 1.0 ± 0.3 | 0.642 |
| Bilirubin (mg/dl) | 0.5 ± 0.2 | 0.8 ± 0.7 | 0.499 |
| Aspartate aminotransferase (IU/L) | 47.3 ± 32.7 | 62.9 ± 31.8 | 0.500 |
| Alanine aminotransferase (IU/L) | 50.3 ± 47.0 | 44.4 ± 24.8 | 0.795 |
| Lactate (mmol/L) | 1.1 ± 0.5 | 1.7 ± 0.8 | 0.271 |
| Pre-decannulation laboratory data | |||
| White blood cell count (B/L) | 14.7 ± 10.9 | 14.5 ± 4.6 | 0.967 |
| Creatinine (mg/dl) | 0.9 ± 0.4 | 1.1 ± 0.6 | 0.617 |
| Bilirubin (mg/dl) | 0.4 ± 0.1 | 0.7 ± 0.1 | 0.003 |
| Aspartate aminotransferase (IU/L) | 42.7 ± 25.1 | 67.6 ± 27.0 | 0.211 |
| Alanine aminotransferase (IU/L) | 39.7 ± 33.1 | 47.6 ± 28.8 | 0.712 |
| Lactate (mmol/L) | 1.3 ± 0.4 | 1.6 ± 0.3 | 0.222 |
| Complications during ECMO | |||
| Acute kidney injury | 0 (0%) | 2 (29%) | 0.301 |
| Acute liver failure | 0 (0%) | 0 (0%) | 1.000 |
| Stroke | 0 (0%) | 0 (0%) | 1.000 |
| Intracranial hemorrhage | 0 (0%) | 0 (0%) | 1.000 |
| Cannula site bleed | 1 (33%) | 0 (0%) | 0.107 |
| GI hemorrhage | 0 (0%) | 1 (14%) | 0.490 |
| SIRS phenomenon | |||
| Fever 24 hours post-decannulation | 3 (100%) | 6 (86%) | 0.490 |
| Leukocytosis 24 hours post-decannulation | 1 (33%) | 2 (29%) | 0.880 |
| New infection | 0 (0%) | 4 (57%) | 0.091 |
| Vasopressor use | 1 (33%) | 5 (71%) | 0.259 |
| Outcomes | |||
| 30-day survival | 2 (66%) | 5 (71%) | 0.880 |
Ninety-five out of 227 patients without COVID-19 developed post-decannulation SIRS. The risk of developing SIRS was not statistically different compared to those with COVID-19 infection (OR 0.70, 95% CI 0.31-1.58; p=0.385). Patients with COVID-19 who developed SIRS tended to be older (56.2 vs. 49.6 years, p=0.039) and on ECMO longer (20.7 vs. 10.7 days, p=0.031) compared to those with SIRS but without COVID-19. Despite this, there was no statistically significant difference in 30-day mortality between these groups (70% vs. 88%, p=0.131). Additionally, there were no other significant differences in other baseline demographics, pre-ECMO vital signs, comorbidities, or listed complications (Table 3).
Table 3. Comparison of patients who experienced systemic inflammatory response syndrome in those with/without preceding COVID-19 infection.
ECMO: extracorporeal membrane oxygenation, VA: venoarterial; VV: veno-venous; FiO2: fraction of inspired oxygen; PEEP: positive end expiratory pressure; SIRS: systemic inflammatory response syndrome
| COVID positive SIRS (n=10) | COVID negative SIRS (n=96) | P-values | |
| Pre-ECMO demographics | |||
| Age (years) | 56.2 ± 8.0 | 49.6 ± 14.3 | 0.039 |
| Male | 7 (70%) | 67 (70%) | 0.989 |
| Body surface area (cm2) | 2.2 ± 0.2 | 2.1 ± 0.3 | 0.999 |
| Body mass index | 35.5 ± 8.0 | 32.2 ± 8.9 | 0.245 |
| ECMO strategy | |||
| VA | 0 (0%) | 63 (66%) | <0.001 |
| VV | 10 (100%) | 23 (34%) | <0.001 |
| Length on ECMO (days) | 20.7 ± 12.3 | 10.7 ± 5.5 | 0.031 |
| Comorbidities | |||
| Smoking history | 1 (10%) | 33 (34%) | 0.116 |
| Coronary artery disease | 0 (0%) | 36 (38%) | 0.017 |
| Diabetes mellitus | 2 (20%) | 22 (23%) | 0.834 |
| Pre-ECMO vital signs | |||
| Temperature (°F) | 99.9 ± 1.5 | 97.9 ± 4.9 | 0.006 |
| Heart rate | 102.1 ± 28.2 | 99.0 ± 36.5 | 0.754 |
| Respiratory rate | 30.3 ± 5.9 | 22.0 ± 8.4 | 0.002 |
| Mean arterial pressure (mm Hg) | 80.1 ± 17.1 | 70.9 ± 24.4 | 0.146 |
| FiO2 (%) | 93.0 ± 14.9 | 93.7 ± 16.7 | 0.891 |
| PEEP (cm) | 14.8 ± 3.6 | 11.5 ± 6.4 | 0.024 |
| Pre-ECMO laboratory data | |||
| White blood cell count (B/L) | 15.7 ± 8.2 | 14.6 ± 7.8 | 0.694 |
| Creatinine (mg/dl) | 1.0 ± 0.3 | 1.6 ± 0.9 | <0.001 |
| Bilirubin (mg/dl) | 0.7 ± 0.6 | 1.2 ± 1.6 | 0.057 |
| Aspartate aminotransferase (IU/L) | 58.2 ± 31.1 | 358.7 ± 1051.1 | 0.006 |
| Alanine aminotransferase (IU/L) | 46.2 ± 30.2 | 277.9 ± 1003.6 | 0.027 |
| Lactate (mmol/L) | 1.5 ± 0.7 | 5.1 ± 4.8 | <0.001 |
| Pre-decannulation laboratory data | |||
| White blood cell count (B/L) | 14.5 ± 6.4 | 15.3 ± 6.4 | 0.715 |
| Creatinine (mg/dl) | 1.1 ± 0.6 | 1.4 ± 1.6 | 0.242 |
| Bilirubin (mg/dl) | 0.6 ± 0.2 | 2.0 ± 2.8 | <0.001 |
| Aspartate aminotransferase (IU/L) | 60.1 ± 27.8 | 67.2 ± 46.7 | 0.489 |
| Alanine aminotransferase (IU/L) | 45.2 ± 28.2 | 64.4 ± 59.8 | 0.092 |
| SIRS phenomenon | |||
| Fever 24 hours post-decannulation | 9 (90%) | 87 (91%) | 0.949 |
| Leukocytosis 24 hours post-decannulation | 3 (30%) | 72 (75%) | 0.003 |
| New infection | 4 (40%) | 37 (39%) | 0.928 |
| Outcomes | |||
| 30-day survival | 7 (70%) | 84 (88%) | 0.131 |
Discussion
This is the first study to further describe the incidence and clinical implications of SIRS following decannulation from ECMO in patients with COVID-19. The clinical correlation between ECMO and systemic inflammation has been well described in the literature [8]. The introduction of blood into an extracorporeal system is known to incite a robust innate humoral and cellular cascade that can closely resemble SIRS. Leukocyte function, complement activation, and endothelial and thrombotic dysregulation are among the many established downstream effects [6-10]. This interplay between coagulation, complement, and endothelial systems initiates and perpetuates a pro-inflammatory cellular and cytokine milieu, which, if unchecked, can lead to vascular and end-organ injury [10-16].
This study demonstrated that SIRS was commonly observed following decannulation from ECMO support, with an overall incidence of approximately 44% in this cohort. The incidence was similar when comparing those with and without concomitant COVID-19 infection. Despite COVID-19 patients being older and enduring longer durations of ECMO support, neither of these variables significantly impacted the incidence of SIRS response or relevant outcomes. It was initially hypothesized that prolonged cannulation would result in endothelial activation, which might sustain pro-inflammatory activation. It was additionally considered that the severe inflammatory state associated with COVID-19 might predispose to more frequent SIRS following decannulation [8]. These data do not confirm either of these hypotheses. It is unclear whether these results could have been mitigated by other variables.
Among those who developed SIRS, patients with COVID-19 tended to have lower creatinine, hepatic aminotransferase, and lactate levels prior to ECMO cannulation. However, there was no sustained difference in these markers prior to decannulation, which may have contributed to comparable rates of SIRS and subsequent 30-day mortality.
When evaluating patients with COVID-19 more closely, we did not identify any pertinent pre-ECMO or pre-decannulation variable, other than age, which was associated with an increased risk of developing post-ECMO SIRS. Advanced age, in contrast to relevant studies in cardiac surgery, was associated with an increased risk of an inflammatory response and resultant SIRS. Despite an older cohort, SIRS was not associated with worse outcomes, which is consistent with a previous study of non-COVID patients at our institution [1]. There was similar use of adjunctive therapies (i.e., tocilizumab, baricitinib, hydroxychloroquine, and glucocorticoids) within two weeks of decannulation in all patients with COVID-19, suggesting no demonstrable impact of these therapies on SIRS in this cohort.
When evaluating the SIRS response further, the majority of patients with COVID-19 developed SIRS in the context of an associated infection, whereas only three patients developed "true SIRS." Unlike our previous experience with post-ECMO SIRS in patients without COVID-19, the development of post-ECMO SIRS with infection was not associated with worse 30-day survival.
Limitations
This study has several limitations owing to its retrospective methodology, small sample size, and single-institution experience. Furthermore, our definition of SIRS included the initiation/escalation of vasopressors, which varies from conventional definitions and excludes patients with associated tachycardia or tachypnea.
Conclusions
Post-ECMO SIRS is common. The incidence of SIRS, whether infectious or not, is similar in COVID patients and non-COVID patients who survive ECMO. Immune-modulation exposure within two weeks of decannulation did not affect the incidence of SIRS in patients with COVID-19.
The authors have declared that no competing interests exist.
Human Ethics
Consent was obtained or waived by all participants in this study
Animal Ethics
Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.
References
- 1.Systemic inflammatory response syndrome (SIRS) after extracorporeal membrane oxygenation (ECMO): Incidence, risks and survivals. Thangappan K, Cavarocchi NC, Baram M, Thoma B, Hirose H. Heart Lung. 2016;45:449–453. doi: 10.1016/j.hrtlng.2016.06.004. [DOI] [PubMed] [Google Scholar]
- 2.ELSO guidelines for patient care, respiratory and cardiac support, ECMO in COVID-19. [ Nov; 2021 ]. 2021. https://www.elso.org/Resources/Guidelines.aspx https://www.elso.org/Resources/Guidelines.aspx
- 3.Extracorporeal membrane oxygenation in cardiopulmonary disease in adults. Abrams D, Combes A, Brodie D. J Am Coll Cardiol. 2014;63:2769–2778. doi: 10.1016/j.jacc.2014.03.046. [DOI] [PubMed] [Google Scholar]
- 4.Extracorporeal Life Support Organization coronavirus disease 2019 interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers. Shekar K, Badulak J, Peek G, et al. ASAIO J. 2020;66:707–721. doi: 10.1097/MAT.0000000000001193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Clinical characteristics of coronavirus disease 2019 in China. Guan WJ, Ni ZY, Hu Y, et al. N Engl J Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Discontinuation of ECMO: a review with a note on Indian scenario. Chakraborty A, Majumdar HS, Das W, Chatterjee D, Sarkar K. Indian J Thorac Cardiovasc Surg. 2023:1–9. doi: 10.1007/s12055-022-01453-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Effect of ex vivo extracorporeal membrane oxygenation flow dynamics on immune response. Ki KK, Passmore MR, Chan CH, et al. Perfusion. 2019;34:5–14. doi: 10.1177/0267659119830012. [DOI] [PubMed] [Google Scholar]
- 8.The inflammatory response to cardiopulmonary bypass: part 1--mechanisms of pathogenesis. Warren OJ, Smith AJ, Alexiou C, et al. J Cardiothorac Vasc Anesth. 2009;23:223–231. doi: 10.1053/j.jvca.2008.08.007. [DOI] [PubMed] [Google Scholar]
- 9.Leukocyte and endothelial activation in a laboratory model of extracorporeal membrane oxygenation (ECMO) Graulich J, Walzog B, Marcinkowski M, et al. Pediatr Res. 2000;48:679–684. doi: 10.1203/00006450-200011000-00021. [DOI] [PubMed] [Google Scholar]
- 10.Rapid activation of the alternative pathway of complement by extracorporeal membrane oxygenation. Vallhonrat H, Swinford RD, Ingelfinger JR, et al. https://journals.lww.com/asaiojournal/Abstract/1999/01000/Rapid_Activation_of_the_Alternative_Pathway_of.25.aspx. ASAIO J. 1999;45:113–114. doi: 10.1097/00002480-199901000-00025. [DOI] [PubMed] [Google Scholar]
- 11.Endothelial cell injury in cardiovascular surgery: the systemic inflammatory response. Boyle EM, Pohlman TH, Johnson MC, Verrier ED. Ann Thorac Surg. 1997;63:277–284. doi: 10.1016/s0003-4975(96)01061-2. [DOI] [PubMed] [Google Scholar]
- 12.Infections and extracorporeal membrane oxygenation: incidence, therapy, and outcome. Haneke F, Schildhauer TA, Schlebes AD, Strauch JT, Swol J. ASAIO J. 2016;62:80–86. doi: 10.1097/MAT.0000000000000308. [DOI] [PubMed] [Google Scholar]
- 13.The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology. Millar JE, Fanning JP, McDonald CI, McAuley DF, Fraser JF. Crit Care. 2016;20:387. doi: 10.1186/s13054-016-1570-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Surface-mediated defense reactions. The plasma contact activation system. Colman RW. J Clin Invest. 1984;73:1249–1253. doi: 10.1172/JCI111326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Inflammatory response to cardiopulmonary bypass. Edmunds LH Jr. Ann Thorac Surg. 1998;5:12–16. doi: 10.1016/s0003-4975(98)00967-9. [DOI] [PubMed] [Google Scholar]
- 16.Complement and the damaging effects of cardiopulmonary bypass. Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. https://pubmed.ncbi.nlm.nih.gov/6606084/ J Thorac Cardiovasc Surg. 1983;86:845–857. [PubMed] [Google Scholar]