Respiratory decompensation due to COVID-19 requiring postpartum extracorporeal membrane oxygenation

Introduction

On March 12th, 2020, the World Health Organization defined the new coronavirus outbreak as a global pandemic. Despite rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it remains unclear how vulnerable the pregnant population is to this global pandemic [1]. In this case report, we present the case of a pregnant woman at 32 weeks 5 days gestation presenting with symptoms consistent with Coronavirus disease 2019 (COVID-19) after numerous negative SARS-CoV-2 PCR results. We discuss the unique clinical obstacles that are specific to the obstetrical population that may impact the disease course in a critically ill pregnant patient with COVID-19.

Case presentation

A 34-year-old G1P0 with a 32 weeks and 5 day live singleton intrauterine gestation presented with four days of worsening dry cough, burning in chest, diarrhea, abdominal pain, subjective fevers, and mild shortness of breath. The patient had previously established prenatal care, with no antepartum issues or pertinent medical history, and a pre-gravid body mass index of 29.8 kg/m². Four days prior to presentation, she was tested for COVID-19 in the setting of new onset respiratory symptoms and known exposure, with negative SARS-CoV-2 PCR results. At that time, she also underwent chest radiography, which demonstrated right infiltrate suspicious for pneumonia.

In the emergency department, the patient was febrile to 38.6 °C, tachycardic to 120 s, normotensive, respiratory rate of 34, initially with oxygen saturation of 90% on room air, requiring 2–3 L/min of supplemental oxygen. Physical exam was notable for diffuse rhonchi. Electrocardiogram showed sinus tachycardia without ischemic changes. Chest radiograph demonstrated a right basilar opacity. Laboratory analysis identified a white blood cell count of 10.9 K/µL with 40% bandememia, normal troponin, mild elevation in aspartate aminotransferase (AST) to 46 U/L and normal alanine aminotransferase (ALT) at 21 U/L and lactate of 0.8 mmol/L. Repeat SARS-CoV-2 PCR was negative. Differential diagnosis included maternal sepsis, and blood and urine cultures were obtained, which resulted negative.

The patient was transferred to Labor and Delivery and was placed in a strict isolation room given continued high clinical suspicion for COVID positive. She was continued on 3 L/min supplemental oxygen via nasal cannula and continuous electronic fetal monitoring was initiated. Antenatal corticosteroids for fetal lung maturity were held given high clinical concern for superimposed bacterial pneumonia and low suspicion for imminent preterm delivery. She was anticoagulated with prophylactic dose subcutaneous heparin and treated with intravenous antibiotic course of Ceftriaxone and Azithromycin per recommendations by infectious disease consult.

The patient was continued on nasal cannula oxygen delivery through hospital day four, with increasing requirements up to 5 L/min. She remained febrile to 39.0–39.4 °C throughout her hospital course, and defervesced with acetaminophen. Repeat SARS-CoV-2 PCR on hospital days four and five again resulted negative. On hospital day five, the patient’s respiratory status rapidly decompensated, over the course of one hour, with oxygen requirements increasing to 15 L on non-re-breather to maintain SpO₂>95%. The patient reported increased shortness of breath, with a respiratory rate in mid 40s, nasal flaring and increased work of breathing noted. Transthoracic echocardiogram demonstrated hyperdynamic left ventricle without evidence of right ventricular dilation. Chest X-ray revealed interval progression of bilateral patchy consolidations involving all lung fields (Figure 1). Lab testing showed while blood cell count of 15.3 K/µL and lactate of 1.0 mmol/L. Attempts to obtain arterial blood gases were made, however with likely venous gases acquired, with pH of 7.37, pCO₂ 25 mmHg, pO₂ 46 mmHg, HCO₃ 14 mmol/L. Tocometer was notable for contractions every 3–4 min, and fetal status remained reassuring. Sterile cervical exam revealed a long and posterior cervix with fingertip dilation.

Figure 1:

Chest radiography on hospital day five demonstrating interval progression of bilateral patchy consolidations involving all lung fields.

At this time, her care involved a multi-disciplinary approach, which included Maternal Fetal Medicine, Critical Care, Infectious Disease, Obstetrical Anesthesia, and Neonatology teams. Given her high risk of further decompensation and intubation, in addition to gestational age of 33 weeks, the decision for delivery was made. Given the patient’s unfavorable cervix and need for urgent but non-emergent delivery, the patient was consented for cesarean section, which was performed under neuraxial anesthesia without complication. The male newborn was assigned Apgars of 8 and 9 at one and five minutes, respectively, birth weight of 1,865 g and umbilical cord gases of 7.25 (venous) and 7.24 (arterial). The newborn was transferred to the NICU on strict isolation precautions, and ultimately tested negative for COVID-19 on day of life two. Throughout her surgery, the patient was maintained on 15 L non-rebreather, with transient desaturations to 85% and tachypnea to 35–45 breaths per minute. The patient was transferred to a COVID designated intensive care unit after completion of the case.

On postoperative day one, SARS-CoV-2 PCR was again conducted with the first positive result. Later that night, the patient was noted to have a significant coughing episode and associated desaturations to SpO₂ 60%. High flow nasal cannula was initiated, however she remained hypoxemic with SpO₂<70% and tachypnic to 50 breaths per minute. Given her acute hypoxemic respiratory failure, the patient was emergently intubated. Post-procedural chest X-ray demonstrated a left sided tension pneumothorax, for which the patient underwent chest tube placement with re-expansion of the lung. Due to refractory hypoxemic and hypercarbic respiratory failure, she was deeply sedated and a neuromuscular blocking agent was initiated. A trial of prone positioning was initiated. Antibiotic coverage was broadened to Vancomycin and Meropenem in the setting of continued high-grade fevers and progressively elevated white blood cell count to 41.6 K/µL. Despite aggressive management, gas exchange remained poor and she met criteria for severe acute respiratory distress syndrome (ARDS) [2], with an arterial blood gas showing a pH of 7.13, partial pressure of arterial carbon dioxide (PaCO₂) of 85 mmHg and partial pressure of arterial oxygen (PaO₂) of 90 mmHg. The following day, she was placed on venovenous extracorporeal membrane oxygenation (ECMO) and transferred to an ECMO center for ongoing management.

Once supported with ECMO, her PaO₂ and PaCO₂ normalized and the ventilator was weaned to facilitate ultra-lung protective ventilation. She was anticoagulated with a continuous infusion of intravenous heparin, weaned off vasopressors and diuresed. She required an additional chest tube for a recurrent left-sided pneumothorax. COVID-19 specific management included a 10-day course of Remdesivir and enrollment in a randomized trial investigating the effect of SARS-CoV-2 convalescent plasma. She was decannulated from ECMO after nine days of support and extubated the following day. Four days following extubation, the patient was weaned from supplemental oxygen via nasal cannula to room air. She continued to receive cardiopulmonary physical therapy and chest tubes were removed after transfer to a step down unit. On postoperative day 19, six days following extubation, the patient was ultimately discharged home.

Discussion

This case highlights the rapid respiratory decompensation and development of severe ARDS in a patient who tested negative for COVID-19 numerous times, and who ultimately required mechanical ventilation and ECMO therapy. Available data suggest that pregnancy itself does not increase the risk of acquiring SARS-CoV-2, and most pregnant mothers recover without undergoing delivery [3]. A recent study demonstrated that, of all pregnant women admitted for delivery at a single institution, 87.9% of those who tested positive were asymptomatic at presentation [4]. In line with recent recommendations put forward by the Society for Maternal Fetal Medicine, this patient warranted in-patient management given hypoxemia below 95% [5]. In this patient, oxygen requirements remained minimal during the first 4 days of admission. It is important to emphasize the possibility of a rapid change in course, even with days of adequate oxygenation and reassuring status.

False negative rates of COVID-19 testing also present a barrier when treating a patient whose clinical status is highly suspicious for SARS-CoV-2 infection. Accuracy and predictive values of the SARS-CoV-2 PCR tests have not yet been systematically evaluated. Regardless of unconfirmed infection with SARS-CoV-2, management should be guided by clinical suspicion, particularly in the pregnant population when early intervention for fetal benefit, such as corticosteroids or magnesium sulfate, can be pursued. The decision in our patient to hold antenatal steroids was based on the concern of worsening respiratory status and low suspicion for risk of preterm birth [5].

Studies suggest that, among patients who develop critical illness, onset of dyspnea is relatively late (median 6.5 days after symptom onset), and progression to ARDS can be swift thereafter (median 2.5 days after onset of dyspnea) [6]. In this patient, progression to severe respiratory deterioration occurred one day after dyspnea, suggesting a faster than average decompensation in a postpartum state. Reduced cardiac and pulmonary reserve during pregnancy, in addition to auto-transfusion attributing to fluid shifts, should be factored into the management approach, particularly when contemplating delivery. Current guidelines state that timing of delivery in pregnant patients with COVID-19 should include individualized delivery criteria in the setting of worsening maternal status [5].

ECMO has been utilized in pregnant and postpartum patients with a variety of conditions, including ARDS, cardiogenic shock, pulmonary embolism, pulmonary hypertension and as extracorporeal cardiopulmonary resuscitation (ECPR) during cardiac arrest [7], [8]. During ECMO, venous blood flows is pumped through a membrane capable of gas exchange in which the blood is oxygenated and carbon dioxide is removed. In cases of venovenous ECMO, the well-oxygenated blood is reinfused to venous system, while arterial reinfusion occurs during venoarterial ECMO. Venovenous ECMO is typically used in cases of ARDS, while venoarterial ECMO is used when cardiac support is required. Based on a recent review of the literature, maternal survival in peripartum patients supported with ECMO ranged from 33 to 77.8% and fetal survival from 50 to 65.1% [9], [10].

The decision to proceed with delivery is multifactorial. Ideally, delivery in a controlled setting following maternal stabilization with a multidisciplinary approach is preferred to optimize both maternal and fetal outcomes. In a non-COVID patient population, a study showed that delivery of respiratory-compromised gravidas requiring ventilatory support resulted in a 28% reduction in fraction of inspired oxygen (FiO₂) within 24 h after delivery. Given the reported patient’s ability to maintain oxygenation with minimal oxygen support via nasal cannula, delivery was initially deferred with the anticipation that the acute maternal illness would resolve with supportive care. As the patient’s oxygen demand increased precipitously, she was deemed at very high risk for intubation and further decompensation. The difficult recommendation was made for delivery for possible improvement in cardio-pulmonary function and avoidance of an emergent delivery. Method of delivery should be weighed with urgency of treatment. Cesarean delivery achieves a more rapid outcome, while vaginal delivery may offer less physical stress in the right candidate. Consideration should be given to antenatal corticosteroids as well in the appropriate clinical setting.

In summary, this case of a 34 year-old with rapid respiratory decompensation at 33 weeks gestation highlights some of the many difficulties healthcare providers encounter when managing COVID-19 in pregnancy. Given the recent emergence of the virus, data and clinical guidelines remain limited. This detailed case report reviews one patient’s unique clinical course in the setting of numerous negative SARS-CoV-2 RT-PCR tests, the multidisciplinary approach to care and use of adjunctive measures such as ECMO to support her recovery from COVID-19.