Extracorporeal membrane oxygenation in pregnancy: a bridge to delivery and pulmonary recovery for COVID-19–related severe respiratory failure

Abstract

SARS-CoV-2 and its clinical disease, COVID-19, are associated with severe maternal respiratory morbidity and mortality in pregnancy.1Hantoushzadeh S. Shamshirsaz A.A. Aleyasin A. et al.Maternal death due to COVID-19.Am J Obstet Gynecol. 2020; 223: 109.e1-109.e16Google Scholar Extracorporeal membrane oxygenation (ECMO) has been used as a bridge to pulmonary recovery in nonpregnant patients,2Shekar K. Badulak J. Peek G. et al.Extracorporeal Life Support Organization Coronavirus Disease 2019 interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers.ASAIO J. 2020; 66: 707-721Google Scholar but there are limited data regarding the management of ECMO in pregnancy. This case series aimed to obtain data on ECMO initiation before delivery in the setting of the ongoing COVID-19 pandemic. All pregnant patients with confirmed COVID-19 based on polymerase chain reaction testing were identified at the University of California, Los Angeles (UCLA) from March 2020 to August 2021, and those who required ECMO were enrolled (institutional review board approval, #20-000579). Case 1 and 2 were previously described.3Douglass K.M. Strobel K.M. Richley M. et al.Maternal-neonatal dyad outcomes of maternal COVID-19 requiring extracorporeal membrane support: a case series.Am J Perinatol. 2021; 38: 82-87Google Scholar The Supplemental Table details institutional protocols for COVID-19, ECMO, and delivery management. COVID-19 therapeutics used include remdesivir (4 of 5), dexamethasone (5 of 5), convalescent plasma (3 of 5), and tocilizumab (2 of 5). All patients were cannulated with 2 veno-venous femoral catheters within 2 days of ventilation and placed on heparin as anticoagulation therapy. The partial pressure of O2 to fraction of inspired O2 ratio at ECMO initiation was 94 (range, 54–109) with a Murray score for acute lung injury of 3.5 (range, 3.3–5.0) and a Respiratory ECMO Survival Prediction Score of 5 (range, 3–6).4Peek G.J. Mugford M. Tiruvoipati R. et al.Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.Lancet. 2009; 374: 1351-1363Google Scholar,5Schmidt M. Bailey M. Sheldrake J. et al.Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score.Am J Respir Crit Care Med. 2014; 189: 1374-1382Google Scholar All neonates received steroids for prematurity and were monitored intermittently unless there was a change in the maternal or fetal status. Of the 25 pregnant patients hospitalized for COVID-19 during the enrollment period, 16 were admitted to the intensive care unit and 5 of them required ECMO for respiratory support. Of those, 4 delivered while on ECMO and 1 was decannulated and discharged with an ongoing pregnancy. All outcomes are presented in the Table and timelines are presented in the Supplemental Figure. Obesity was a risk factor for 5 of 5 patients and 3 of 5 patients belonged to the Black, indigenous, people of color group. ECMO was initiated at a median of 25 weeks and 6 days of gestation. The total median time on ECMO was 11 days (range, 10–68) with 10 days (range, 1–32) of ECMO antepartum. The most common complications occurred in 4 of 5 cases, namely pressor use, infection, venous thromboembolism, and bleeding including postoperative hematomas, disseminated intravascular coagulation, and delayed postpartum hemorrhage. Hematologic morbidity occurred within days of cesarean birth and or decannulation. The median gestational age at birth was 29 weeks 3 days (range, 26 weeks 5 days to 31 weeks 6 days) and all deliveries were by cesarean delivery for a wide range of maternal and fetal indications with 4 of 4 livebirths and neonatal survival to discharge. There was significant neonatal respiratory morbidity with a median neonatal intensive care unit length of stay of 58 days (range, 31–58). The maternal survival to delivery and discharge was 5 of 5, with a total median length of stay of 30 days (range, 16–80). Postpartum mood disorder was commonly diagnosed by psychiatry (3 of 4 cases) and breastfeeding occurred in 1 patient.TableUse of extracorporeal membrane oxygenation in pregnancy for COVID-19–related respiratory failure and associated outcomesDemographicsMonth of admissionMedian (range) or N %Case 1July 2020Case 2July 2020Case 3Jan. 2021Case 4June 2021Case 5July 2021Jan. 2021(July 2020 to July 2021)Age (y)33(27–43)2743303433Body mass index (kg/m2)36(30–45)3635453630Gravidity2(2–3)32223Parity1(0–1)00111Previous OB history480%NoCD × 1, PPROMCD × 1CD × 1CD × 1Race (non-White)360%BlackLatinxLatinxWhiteWhiteHealth insurance (public)240%PublicManaged carePublicPrivatePrivateHypertensive disease240%PreeclampsiaChronicNoNoNoDiabetes120%NoGestationalNoNoNoPulmonary disorders00%NoNoNoNoNoOther medical problems240%NoNoHypothyroidismHypothyroidismNoECMO outcomesGestational age at ECMO initiation25wk6d(24wk6d–30wk5d)30wk5d26wk5d24wk6d25wk1d25wk6dTotal ECMO length (d)11(10–68)118416810Length of antepartum ECMOaECMO antepartum time was <1 day (17 hours), rounded up to 1 day. (d)10(1–32)81aECMO antepartum time was <1 day (17 hours), rounded up to 1 day.322910Birth to decannulation (d)8.5(3–39)38939—Extubation while on ECMO120%NoNoNoNoYesMobilization while on ECMO240%NoNoNoYesYesECMO complicationsCircuit exchanges0(0–4)00140Pressor use480%NoYesYesYesYesAntihypertensive use360%YesNoYesYesNoCardiac120%NoNoNoHeart block, cardiac arrestNoLung240%Bronchoscopy mucus plugNoNoPneumothoraxNoInfectious480%Pseudomonas pneumoniaPseudomonas pneumoniaESBL UTI and pneumoniaCanula site infectionNoRenal120%Acute kidney injuryNoNoNoNoLiver120%NoNoHELLPNoNoGastrointestinal360%NoDysphagiaLower bleedLower bleedNoNeurologic00%NoNoNoNoNoAnticoagulation agent (addition to heparin)360%HeparinHeparinHeparin then argatrobanHeparin then argatrobanheparin then argatrobanVenous thromboembolism480%NoLeft popliteal to common femoral and pulmonary embolismBilateral external iliac, inferior vena cava, right brachialRight common femoralLeft gastrocnemiusBleeding complication480%Disseminated intravascular coagulationNoAnterior rectus and uterine hematomas, delayed postpartum hemorrhageRectus hematoma, postpartum abdominal wash-out and inferior epigastric embolizationHemolytic anemia with thrombocytopenia Red cells12(0–48)12242480 Plasma0(0–4)00040 Platelets1(0–2)2021 Cryoprecipitate1(0–2)10121Anticoagulation at discharge480%NoYes, apixabanYes, enoxaparinYes, apixabanYes, enoxaparinNeonatal outcomesGestational age at birth29wk3d(26wk5d-31wk6d)31wk6d26wk5d29wk3d29wk2d—Mode of delivery (CD)4100%Emergent cesareanEmergent cesareanPlanned cesareanPlanned cesarean—Indication for deliveryNANAConcern for HELLP vs abruptionPreterm laborImproving maternal status so delivery to facilitate decannulationMaternal cardiac arrest with worsening status—1-minute Apgar score2.5(1–4)4123—5-minute Apgar score6(5–9)7559—UA pH7.36(7.23–7.41)NA7.237.367.41—UA base excess5(1-5)NA155—Live birth4100%YesYesYesYes—Birthweight (g)1234(1000–1465)1465100011941274—NICU length of stay (d)58(31–58)31NA6558—Neonatal morbidityNANAVentilation, bradycardiaVentilation, persistent ductusSepsis, chronic lung disease persistent ductusRespiratory distress syndrome, anemia—Neonatal survival to discharge4100%YesYesYesYes—Positive COVID-19 PCR00%NoNoNoNo—COVID-19+ antibodies125%YesNoNoNo—Maternal outcomesSurvival to delivery4100%YesYesYesYes—Survival to discharge5100%YesYesYesYesYesTracheostomy (d)10(0–113)160101130Discharged on O2240%NoNoNoYesYesDischarge with rehabilitation120%NoNoYesNoNoTotal length of stay (d)30(16–80)3016558017ICU length of stay (d)26(11–77)2611497712Postpartum mood disorder375%DepressionNoAnxietyInsomnia—Breastfeeding125%NoNoPumping POD1-POD5, POD11No—Neonatal outcomes for case 5 were not available because the pregnancy was ongoing at time of discharge.CD, cesarean delivery; ECMO, extracorporeal membrane oxygenation; ESBL, extended spectrum beta lactamase; HELLP, hemolysis, elevated liver enzymes, low platelets syndrome; ICU, intensive care unit; POD, postoperative day; PPROM, preterm premature rupture of membranes; UA, umbilical arterial; UTI, urinary tract infection.Yin. Extracorporeal membrane oxygenation in pregnancy for severe respiratory failure in COVID-19. Am J Obstet Gynecol 2022.a ECMO antepartum time was <1 day (17 hours), rounded up to 1 day. Open table in a new tab Neonatal outcomes for case 5 were not available because the pregnancy was ongoing at time of discharge. CD, cesarean delivery; ECMO, extracorporeal membrane oxygenation; ESBL, extended spectrum beta lactamase; HELLP, hemolysis, elevated liver enzymes, low platelets syndrome; ICU, intensive care unit; POD, postoperative day; PPROM, preterm premature rupture of membranes; UA, umbilical arterial; UTI, urinary tract infection. Yin. Extracorporeal membrane oxygenation in pregnancy for severe respiratory failure in COVID-19. Am J Obstet Gynecol 2022. This case series presents outcomes for the use of ECMO during pregnancy for acute respiratory failure caused by COVID-19. Our findings concur with the 2 other cases in literature,6Barrantes J.H. Ortoleva J. O’Neil E.R. et al.Successful treatment of pregnant and postpartum women with severe COVID-19 associated acute respiratory distress syndrome with extracorporeal membrane oxygenation.ASAIO J. 2021; 67: 132-136Google Scholar showing that pregnancy can be prolonged on ECMO, delivery on ECMO can be performed safely, and ECMO can serve as a bridge to maternal respiratory recovery. There were high rates of maternal and neonatal survival. Significant hematologic morbidity and neonatal respiratory morbidity were observed. ECMO in pregnancy should be managed with an experienced multidisciplinary team that can make key decisions about initiation, cannulation, timing of delivery, management of complications, and postpartum care.