Outcomes of Veno-Venous Extracorporeal Membrane Oxygenation in Patients with Severe Acute Respiratory Distress Syndrome (ARDS) Infected with SARS-nCoV2 infection.

DOI: https://doi.org/10.21203/rs.3.rs-1909331/v1

Abstract

Background:

Veno Venous Extra Corporeal Membrane Oxygenation (VV-ECMO) in patients with severe acute respiratory syndrome infected with the novel coronavirus SARS-nCoV2.

Patients & Methods:

Adult patients with age more than 18 years on VV ECMO were evaluated on the duration of the onset of symptoms to hospital admissions (direct or referred), mechanical ventilation (MV), time to initiate ECMO, Murray score, PaCO2, and PaO2/FiO2 ratio, associated organ injury, duration of ICU, Hospital stay and mortality.

Results:

From 01 June 20 to 30 May 2022, 8 patients were placed on Veno-Venous Extra Corporeal membrane oxygenation (VV-ECMO). The mean age of cannulation was 46 years with 25% (2) being healthcare workers. The mean Murray score, PaCO2, and the PaO2 / FiO2 ratio were 3.375, 72.5 mmHg, and 65.98 respectively. The average time to initiate ECMO was 8.375 days from the time of admission, with an average duration of ECMO of 16.375 days. One (12.5%) survived the intervention and was discharged uneventfully.

Conclusions:

Early referral and initiation of VV-ECMO in severe SARS-nCoV2 ARDS may improve outcomes.

Introduction:

Veno-venous Extra Corporeal membrane oxygenation (VV-ECMO) is an adjunctive device used for the correction of severe hypoxia secondary to severe acute respiratory distress syndrome (ARDS) and is recommended by the World Health Organization (WHO) and the Extracorporeal Life Support Organization (ELSO) for the management of severe SARS-nCoV2 pulmonary infection as a bridge to recovery or a bridge to lung transplant (1, 2).

Methods:

Eight patients were placed on VV ECMO during the covid pandemic for severe SARS-nCoV2 ARDS diagnosed with RT-PCR during the period from 01 June 2020 to 30 May 2022, which were admissions direct or referred. Data were collected retrospectively from the hospital's electronic health records after approval by the hospital ethics committee with a waiver of consent due to the ongoing pandemic.

All Patients on VV-ECMO had received intravenous dexamethasone, Remdesivir, Tocilizumab, low molecular weight heparin, and antibiotics based on the culture sensitivity, along with oxygen support with variable or fixed oxygen delivery devices e.g., High flow nasal oxygen (HFNO) and with Non-invasive ventilation (NIV) support based on the clinical condition of the patients. If the patient had deteriorated despite the optimal medical treatment described above, the patients were intubated and ventilated using volume control mode (VCV) using lung protection ventilation (LPV) strategies, and they were also ventilated in a prone position if the PaO2/FiO2 ratio was < 150. After excluding the contraindications for ECMO i.e., history of stroke with neurological deficits, malignancies, end-stage renal disease, mechanical ventilation for more than 14 days, patients on high doses of vasopressors a decision to initiate ECMO was done by the intensivist after explaining the risks vs benefits to the patient relatives and written informed consent was taken either telephonically or through video conference.

During the initial phases of the pandemic, there was an acute surge of patients, and due to a lack of adequate resources and ethical issues such as distributive justice, a very limited number of patients were selected for ECMO placement. The Criteria for initiation of ECMO were strictly based on the EOLIA trial, if a patient was in hypoxic respiratory failure despite optimal ventilation strategies that are, respiratory rate > 35/min, tidal volume of 6ml/kg of predicted body weight, Plateau pressures greater than 32 cm H2O, PEEP > 10 cm H2O, FiO2 > 80%, with a PaO2/FiO2 ratio of < 50 mmHg for at least 3h, or a PaO2/FiO2 ratio of < 80 mmHg for at least 6 h or an arterial blood gas (ABG) showing a pH of < 7.25 with a paCO2 ≥ 60 mmHg for at least 6 h with anticipated prolonged ventilation for > 7 days and a Murray score of > 3 with a single organ failure (3). Appropriate personal protective equipment (PPE) was used with a restricted entry to the number of people during the cannulation procedure. A 2D echocardiography was done before cannulation for evaluating the right and left ventricular dysfunction,

The usual site for cannulation was in the right femoral vein for the drainage with a return cannula placed in the right internal jugular vein (IJV). The size of cannulas selected was dependent on the height, weight, and body surface area (BSA) of the patient. A size 22 to 27 Fr was used for drainage along with a size 17–21 Fr for the placement of the return cannula.

Percutaneous placement of the cannula was done using Seldinger’s technique ultrasonography (USG). A 2D echocardiography was used to correct the placement of the guidewire and a 15 cm distance was maintained between the drainage and the return cannulas to prevent recirculation. Femoral-femoral cannulation was used only in one patient and was unviable due to the increased risk of recirculation and worsening of gas exchange. The flow rate was titrated by controlling the rpm on the ECMO console to maintain a flow of 60–80 ml/kg/min to improve oxygenation, with the sweep gas flow adjusted accordingly. Intravenous bolus heparin was used at a dose of 60–80 units per kg body weight after both the guide wires were inside, which was followed by a continuous infusion with a target ACT of 180–220 seconds or APTT target of 60–80 seconds. The tests were carried out at regular intervals to maintain an optimal level of anticoagulation. Sedation and paralysis were down-titrated as tolerated by the patients. Daily arterial blood gas was performed to titer the sweep gas and FiO2. Serial measurements of reactive C protein, D dimer, lactate dehydrogenase (LDH), and procalcitonin were also done every 48- 72h. The withdrawal from VV ECMO was performed if the patient remained stable with a fresh gas flow of 0 L/min for at least 4–6 hours or was left to the discretion of the intensivist.

Statistical analysis

Continuous variables are presented as median (interquartile range [IQR]), while categorical variables are expressed as percentages (%). Statistical analyses are done using MS excel.

Results:

A total of 298 patients were admitted to the Covid ICU for mechanical ventilatory support, of which 08 (2.68%) patients were placed on VV ECMO. Patients had a FiO2 of 1.0 with a PEEP of 10 cm H2O at the time of cannulation. The mean age of the patients was 46 years with a male preponderance of 6(75%). The mean time from the onset of symptoms and the initiation of VV ECMO was 15 days, with an average of 8.375 days for the initiation of ECMO after hospital admission. The Common comorbidities that were seen are obesity, hypertension, and diabetes which were seen in 5(62.5%) patients. Six (75%) patients were referred from other hospitals with a mean duration of 5.85 days and were initially managed with HFNO/ NIV support with a mean duration of 4.25 days before intubation and mechanical ventilation. The mean time to initiate mechanical ventilation was 06 days. Post intubation patients were sedated and paralyzed using intravenous fentanyl and atracurium/cisatracurium infusions and were ventilated in the prone position for 18-24 hours/day for 3-4 days. The mean duration of pronation was 3.25 days. The median Murray score, PaCO2, and the PaO2 / FiO2 ratio were 3.375, 72.5 mmHg, and 65.98 respectively (See Figure:1). The trends in respiratory parameters are shown in (Figure 2).

Percutaneous tracheostomy was performed with a mean of 07 days. The average duration of stay at ECMO was 16.375 days. Acute right ventricular dysfunction was present in 04(50%) patients before initiation of the ECMO cannulation

Complications:

The most common complications were acute kidney injury, which occurred in 7 (87.5%) patients, of which 4 (50%) required continuous Veno-Veno hemodiafiltration (CVVHDF) with 4 (50%) patients developing sepsis with multiorgan failure secondary to nosocomial pneumonia. Two (25%) patients had pulmonary bleeding that required frequent bronchoscopies and cryotherapy. Two (25%) patients had circuit and oxygenator thrombosis within 24 hours and 12 days respectively after the initiation of ECMO. Four (50%) patients had bleeding at the cannula and tracheostomy site secondary to disseminated intravascular coagulation which was managed with blood and component therapy.

Discussion:

Mortality in critically ill patients with severe SARS-nCoV2 was reported to be greater than 50% according to available data(4). The management of severe refractory hypoxemia with conventional mechanical ventilation despite optimal utilization of FiO2, positive end-expiratory pressure (PEEP), neuromuscular blockade, and prone positioning was limited (5, 6). The use of VV -ECMO in the previous pandemics such as H1N1 and MERS (Middle East respiratory syndrome)-CoV infection, had shown promising results (5).

Early initiation of the VV-ECMO (3 interquartile range (IQR) 2–5 days) when compared to late (0.5 interquartile range (IQR) 0–1 days) had shown improved mortality, which was 8.375 days in our series (7). Mortality in covid-ECMO patients ranged from 30 to 95% when initiated late due to resource limitations (trained personnel, delayed transport/ referral to designated centers, and ethical considerations) in addition to patients decompensating before initiation due to progressive lung fibrosis (8). Prolonged mechanical ventilation beyond 6.5 days and initiation of ECMO in patients on mechanical ventilation beyond 07 days have shown poor outcomes(9). Acute right ventricular dysfunction before initiation of ECMO was also shown to have a worse outcome with increased mortality, which was present in 4 (50%) patients in our series (10). VV ECMO allows ultralow lung-protective ventilation thereby preventing barotrauma, that is, pneumothorax and pneumomediastinum, volutrauma, and atelectotrauma(11, 12). Our mean time to initiate ECMO from the onset of symptoms was 15 days, with a mean of 8.375 days after hospital admission which, compared to available data, had shown mixed results when initiated early with a median time of 14 days from the onset of symptoms (13, 14). During the initial phase of the pandemic, the initiation of ECMO was controversial due to ethical and legal aspects in already constrained resource settings. No head-to-head randomized clinical trials were conducted comparing invasive mechanical ventilation with or without ECMO support(15). Depending on the age, the severity of hypoxemia, duration and intensity of mechanical ventilation, and a PaO2/FiO2 ratio of < 80 mmHg early initiation of ECMO had shown a reduction in mortality of 7.1% when compared to mechanical ventilation alone(16). Early VV-ECMO is an alternative salvage therapy as a recovery or bridge to lung transplant and was shown to improve the outcomes and decrease mortality, especially in ECMO-designated centers (11, 17). The prolonged duration of mechanical ventilation before ECMO placement had been shown to have worse outcomes(18). The World Health Organization (WHO) during the pandemic in its interim guidelines had included ECMO as rescue therapy in patients who did not improve on conventional mechanical ventilation (19). A recent systematic review and meta-analysis on the role of ECMO have shown mortality of 37% in covid patients, which was similar to non-covid patients, giving an impetus to start early(20). Our patient population was sicker with more than 80% risk of death, and with late referrals and ethical issues, there was increased mortality (21). The complications seen in our cases were similar to other studies.

Limitations

Data were retrospectively collected during the pandemic in limited resource settings, and the majority of cases were referred late with severe ARDS. With finite resources, trained personnel, and ethical issues during the initial phase of the pandemic, most of the patients could not receive these lifesaving therapies.

Conclusions:

Strict criteria in patient selection and ethical considerations for early intervention with VV ECMO as a rescue strategy in SARS-nCov2 respiratory failure might improve the outcome.

Declarations:

1. Funding: Not Applicable

2. Conflicts of interest/Competing interests: The authors declare no competing interests.

3. Ethics approval (include appropriate approvals or waivers): Institutional Ethical committee (Army Hospital Research and Referral, New Delhi) approval.

4. Consent to participate: Waiver Obtained due to ongoing pandemic.

5. Consent for publication: Taken from the Head of the institution.

6. Availability of data and material: Available with the corresponding author.

7. Code availability: not applicable

8. Authors' contributions: Directly involved in collecting, editing, and analysis of the data.

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